Protein-Ligand Interaction (PLIO) is an ontology focused on protein-ligand interactions at micro-scale level and it captures the key areas of knowledge describing parameters and forces involved in protein-ligand interactions. Ontology1271664172453:Affinity Wermuth, C.G., et al., Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998). Pure Appl. Chem., 1998. 70(5): p. 1129-1143. affinity affinities binding affinity binding affinities receptor ligand affinity bioaffinity Affinity is the tendency of a molecule to associate with another. The affinity of a drug is its ability to bind to its biological target (receptor, enzyme, transport system, etc.) For pharmacological receptors it can be thought of as the frequency with which the drug, when brought into the proximity of a receptor by diffusion, will reside at a position of minimum free energy within the force field of that receptor. For an agonist (or for an antagonist) the numerical representation of affinity is the reciprocal of the equilibrium dissociation constant of the ligand-receptor complex denoted K A, calculated as the rate constant for offset (k -1) divided by the rate constant for onset (k 1). Ontology1271664172453:Agonist http://www.chemistry-dictionary.com/definition/agonist.php agonist agonists AG AGON agonism An agonist is an endogenous substance or a drug that can interact with a receptor and initiate a physiological or a pharmacological response characteristic of that receptor (contraction, relaxation, secretion, enzyme activation, etc.). Ontology1271664172453:Allosteric_agonists http://pharmrev.aspetjournals.org/content/55/4/597/T1.expansion allosteric agonist allosteric agonists allotopic agonists allotopic agonist allosteric agonism Allosteric (allotopic) agonists or activators are ligands that are able to mediate receptor activation in their own right by binding to a recognition domain on the receptor macromolecule that is distinct from the primary (orthosteric) site. Neutral allosteric (allotopic) ligands bind to an allosteric site without affecting the binding or function of orthosteric ligands but can still block the action of other allosteric modulators that act via the same allosteric site. Ontology1271664172453:Allosteric_enhancer Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. allosteric enhancer allosteric enhancers allotopic enhancer allotopic enhancers Allosteric (allotopic) enhancers are modulators that enhance orthosteric ligand affinity and/or agonist efficacy while having no effect on their own. Ontology1271664172453:Allosteric_interaction Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. allosteric interaction allosteric interactions allotopic interaction allotopic interactions An interaction between ligands that bind to distinct, non-overlapping, recognition sites on the receptor macromolecule. Accordingly, the term allotopic can be used interchangeably with the term allosteric when describing cross-interactions between different sites on a receptor macromolecule. Ontology1271664172453:Antagonist C.G Wermuth, et al., Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998). Pure Appl. Chem., 1998. 70(5): p. 1129-1143. antagonist antagonists antagonism An antagonist is a drug or a compound that opposes the physiological effects of another. At the receptor level, it is a chemical entity that opposes the receptor-associated responses normally induced by another bioactive agent. Ontology1271664172453:Aromatic-Aromatic_Interaction http://pipe.ibibiosolutions.com/Aromatic-Aromatic.html aromatic-aromatic interaction aromatic-aromatic interactions aromatic/aromatic stacking interactions pi-pi interaction p-p interaction pi stacking pi-stacking pi/pi stacking p-stacking arene arene pi-stacking interactions aromatic stacking pi stacking interaction pi stacking interactions pi-stack The electrons of the aromatic rings are localised on both sides of the flat ring, so that there is a small partial negative charge on the face, and a small partial positive charge on the hydrogens on the edge, which gives the possibility of electrostatic interactions. This type of interaction is present between side chains of 50-60% of the aromatic amino acids. Side chain aromatic rings tend to stack with edge to face at an angle of 60-90° in about 2 out of 3 interactions; when they stack face to face the rings are offset so that the partial charges may interact. The binding energy is of the order of 1-2 kcal mol-1. The contribution of free energy to protein stability is estimated to be relatively small and of the order of 0.6-1.3 kcal mol-1. Ontology1271664172453:Atomic_force_microscopy http://www.oxfordreference.com/views/ENTRY.html?entry=t83.e183&srn=1&ssid=676696497#FIRSTHIT http://www.nlm.nih.gov/mesh/ Atomic Force Microscopy Microscopy, Atomic Force Scanning Force Microscopy Force Microscopies Force microscopy AFM Atomic force microscopy (AFM) A type of atomic probe microscopy in which a small probe, consisting of a tiny chip of diamond, is held on a spring-loaded cantilever in contact with the surface of the sample. The probe is moved slowly across the surface and the tracking force between the tip and the surface is monitored. The probe is raised and lowered so as to keep this force constant, and a profile of the surface is produced. Scanning the probe over the sample gives a computer-generated contour map of the surface. A type of scanning probe microscopy in which a probe systematically rides across the surface of a sample being scanned in a raster pattern. The vertical position is recorded as a spring attached to the probe rises and falls in response to peaks and valleys on the surface. These deflections produce a topographic map of the sample. Ontology1271664172453:Average_ionization_energy http://www.codessa-pro.com/descriptors/electrostatic/aie.htm Average ionization energy I(r)=(Σρ(r)ε)/ρ(r) Σ - sum is over i ρ(r) - electron density of ith molecular orbital at the point r ε - ith molecular orbital energy Ontology1271664172453:BFGC http://en.wikipedia.org/wiki/BFGS_method BFGC Broyden Fletcher Goldfarb Shanno method L-BFGS The Broyden–Fletcher–Goldfarb–Shanno (BFGS) method is a method for solving nonlinear optimization problems (which lack constraints). The BFGS method approximates Newton's method, a class of hill-climbing optimization techniques that seeks a stationary point of a (twice continuously differentiable) function: For such problems, a necessary condition for optimality is that the gradient be zero. Newton's method and the BFGS methods need not converge unless the function have a quadratic Taylor expansion near an optimum. These methods use the first and second derivatives. Ontology1271664172453:Balaban_J_index http://www.codessa-pro.com/descriptors/topo/balaban.htm Balaban J index Balaban's J index J=(q/μ+1)Σ(SiSj)-1/2 q - number of edges in the molecular graph m = (q – n + 1) - the cyclomatic number of the molecular graph n – number of atoms in the molecular graph Si - distance sums calculated as the sums over the rows or columns of the topological distance matrix of the molecule, D. (SiSj)-1/2 means that (SiSj) is in the power of -1/2 Σ(SiSj)-1/2 sum is overedges ij Ontology1271664172453:Binding_selectivity http://en.wikipedia.org/wiki/Binding_selectivity#cite_note-0 binding selectivity binding selectivities selectivity of the binding Binding selectivity refers to the differing affinities with which different ligands bind to a substrate forming a complex. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate. Ontology1271664172453:Bivalent_cooperative_binding bivalent cooperative binding bivalent binding Ontology1271664172453:Bonded_Interaction http://www.chem.ufl.edu/~itl/2045/lectures/lec_g.html bonded interaction bonded interactions Bonded interaction is interaction between atoms which are linked by chemical bond. Ontology1271664172453:Bonding_information_content_index http://www.codessa-pro.com/descriptors/topo/bici.htm Bonding information content index IC=-Σ((ni/n)*log2(ni/n)) BIC=IC/(log2(q)) bonding information content index ni - number of atoms in the ith class n - the total number of atoms in the molecule k - number of atomic layers in the coordination sphere around a given atom q - number of edges in the molecular graph Σ((ni/n)*log2(ni/n)) - sum is from i=1 till k log2(q)) - logarithm of q to base 2 log2(ni/n)- logarithm of ni/n to base 2 Ontology1271664172453:Cation-Pi_Interaction http://pipe.ibibiosolutions.com/Cation-Pi.html Cation-pi interaction Cation-pi interactions Cation-p interaction is a noncovalent molecular interaction between the face of an electron-rich p system (e.g. benzene, ethylene) with an adjacent cation (e.g. Li+, Na+). This unusual interaction is an example of noncovalent bonding between a monopole (cation) and a quadrupole (p system). Cation-p interaction energies are of the same order of magnitude as hydrogen bonds or salt bridges and play an important role in molecular recognition. Ontology1271664172453:Cavity_depth cavity depth depth of cavity Ontology1271664172453:Cavity_shape cavity shape shape of cavity Molecular cavity shape Ontology1271664172453:Cavity_size cavity size size of cavity Ontology1271664172453:Circular_dichroism http://www.photophysics.com/circulardichroism.php Circular dichroism CD Circular dichroism is the difference in the absorption of left-handed circularly polarised light (L-CPL) and right-handed circularly polarised light (R-CPL) and occurs when a molecule contains one or more chiral chromophores (light-absorbing groups). Circular dichroism = ΔA(λ) = A(λ)LCPL - A(λ)RCPL, where λ is the wavelength. Circular dichroism (CD) spectroscopy is a spectroscopic technique where the CD of molecules is measured over a range of wavelengths. CD spectroscopy is used extensively to study chiral molecules of all types and sizes, but it is in the study of large biological molecules where it finds its most important applications. A primary use is in analysing the secondary structure or conformation of macromolecules, particularly proteins, and because secondary structure is sensitive to its environment, e.g. temperature or pH, circular dichroism can be used to observe how secondary structure changes with environmental conditions or on interaction with other molecules. Structural, kinetic and thermodynamic information about macromolecules can be derived from circular dichroism spectroscopy.Measurements carried out in the visible and ultra-violet region of the electro-magnetic spectrum monitor electronic transitions, and, if the molecule under study contains chiral chromophores then one CPL state will be absorbed to a greater extent than the other and the CD signal over the corresponding wavelengths will be non-zero. Ontology1271664172453:Clique-search-based_method Rarey, M., Protein-Ligand Docking, GMD - German National Research Center for Information Technology, Institute for Algorithms and Scientific Computing (SCAI): 53754 Sankt Augustin, Germany. http://www.cs.cmu.edu/~blmt/Seminar/SeminarMaterials/interactions.html Clique-search based method Clique-search based methods Clique-search based approaches Clique-search based approach clique matching Clique-search based approaches Matching characteristic features of the two molecules (Kuhl, Crippen, Friesen (1984) J. Computational Chemistry 5, 24-34) use a graph to search for compatible matches: the vertices of the graph are all possible matches and edges connect pairs of vertices representing compatible matches compatibility = distance compatibility with in a fixed tolerance epsilon The matches (p1,l1), (p2,l2) are distance-compatible if |d(p1,p2)-d(l1,l2)|<epsilon Ontology1271664172453:CoMFA http://www.chem.qmul.ac.uk/iupac/medchem/ah.html#c11 Taboureau, O., 3D descriptors and fingerprints, Chemoinformatics, CBS-BioCentrum. CoMFA Comparative molecular field analysis Comparative molecular field analysis (CoMFA) is a 3D-QSAR method that uses statistical correlation techniques for the analysis of the quantitative relationship between the biological activity of a set of compounds with a specified alignment, and their three-dimensional electronic and steric properties. CoMFA: Comparative Molecular Field Analysis. Determines the electrostatic and steric interaction energy between a probe and the molecule separately Ontology1271664172453:Competitive_antagonism Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606 competitive antagonism competitive antagonist competitive antagonists In competitive antagonism, the binding of agonist and antagonist is mutually exclusive. This may be because the agonist and antagonist compete for the same binding site or combine with adjacent sites that overlap (syntopic interaction). A third possibility is that different sites are involved but that they influence the receptor macromolecule in such a way that agonist and antagonist molecules cannot be bound at the same time. Ontology1271664172453:Complementary_information_content_index http://www.codessa-pro.com/descriptors/topo/cici.htm Complementary information content index IC=-Σ((ni/n)*log2(ni/n)) CIC=log2(n) -IC Complementary information content index ni - number of atoms in the ith class n - the total number of atoms in the molecule k - number of atomic layers in the coordination sphere around a given atom Σ((ni/n)*log2(ni/n)) - sum is from i=1 till k log2(ni/n)- logarithm of ni/n to base 2 log2(n) - logarithm of n to base 2 Ontology1271664172453:Complex-Based_Pharmacophore complex-based pharmacophore complex-based pharmacophores ligand-receptor complex structure-based pharmacophore complex structure-based pharmacophore The pharmacophore is determined from protein-ligand complex(es). Ontology1271664172453:Conjugate_gradient http://research.chem.psu.edu/shsgroup/chem647/newNotes/node7.html http://chsfpc5.chem.ncsu.edu/~franzen/CH795N/lecture/IV/IV.html Mager, P.P., A. Weber, and P. Illes, Bridging the gap between structural bioinformatics and receptor research: the membrane-embedded, ligand-gated, P2X glycoprotein receptor. Curr Top Med Chem, 2004. 4(16): p. 1657-705. Conjugate gradient Conjugate gradient minimization conjugate gradient minimizer First-order minimization method. The conjugate gradient technique uses information from previous first derivatives to determine the optimum direction for a line search. Produces a set of mutually conjugate directions so that each successive step continually refines the direction toward the minimum (without oscillations). Disadvantages: -requires full convergence for each line search .More functional evaluations per iteration. -for nonharmonic systems can get stuck (i.e. if start far from minimum) Advantage: more efficient convergence to minimum -number of iterations smaller than for steepest descents. Ontology1271664172453:Constitutional_Descriptors_ http://www.vcclab.org/lab/indexhlp/consdes.html constitutional descriptors constitutional descriptor Descriptors, independent from molecular connectivity and conformations. Ontology1271664172453:Continuant_Entity Basic Formal Ontology Version 1.1: http://www.ifomis.org/bfo/1.1/snap#Continuant Endurant An entity [bfo:Entity] that exists in full at any time in which it exists at all, persists through time while maintaining its identity and has no temporal parts.. Ontology1271664172453:Covalent_bonding http://library.thinkquest.org/C005377/content/glossary.htm covalent bonding covalent bond covalent bonds The chemical bond formed by the sharing of a pair of electrons by two atoms . Each bonded atom contributes one electron towards the shared pair. Ontology1271664172453:Dipole_moment http://www.shodor.org/chemviz/glossary.html http://www.chemistry.mcmaster.ca/esam/Chapter_7/section_3.html Dipole moment dipole moment is denoted by μ=QR μ - dipole moment Q - charge R - distance Dipole moment is measured in debyes. Ontology1271664172453:Distance_geometry http://www.cs.cmu.edu/~blmt/Seminar/SeminarMaterials/interactions.html distance geometry geometry algorithm Distance geometry - comes from NMR - instead of describing a molecule by coordinates in Euclidean space, it is described by a distance matrix, containing all interatomic distances based on distance matrices, a set of conformations can be described in a comprehensive form by calculating a distance interval for each atom pair - uses clique search and distance compatibility: two matches between protein and ligand atoms are compatible if the site point distances lies within the distance interval of the ligand atom pair - drawback: the distance matrix is over-determined Ontology1271664172453:Disulfide_Interaction http://pipe.ibibiosolutions.com/Disulfide.html disulfide interaction disulfide interactions disulfide bond A disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore C-S-S-C. The disulfide bond is strong, a typical bond dissociation energy being 60 kcal/mole. Being about 40% weaker than C-C and C-H bonds, the disulfide bond is thus often the "weak link" in many molecules. The disulfide bond is about 2.05Å in length, about 0.5Å longer than a C-C bond. Rotation about the S-S axis is subject to a low barrier. Disulfides show a distinct preference for dihedral angles approaching 90°. When the angle approaches 0° or 180°, then the disulfide is a significantly better oxidant. Disulfide bonds in proteins are formed between the thiol groups of cysteine residues. The other sulfur-containing amino acid, methionine, cannot form disulfide bonds. he disulfide bond stabilizes the folded form of a protein in several ways: 1) It holds two portions of the protein together, biasing the protein towards the folded topology. Stated differently, the disulfide bond destabilizes the unfolded form of the protein by lowering its entropy. 2) The disulfide bond may form the nucleus of a hydrophobic core of the folded protein, i.e., local hydrophobic residues may condense around the disulfide bond and onto each other through hydrophobic interactions. 3) Related to #1 and #2, the disulfide bond link two segments of the protein chain, the disulfide bond increases the effective local concentration of protein residues and lowers the effective local concentration of water molecules. Since water molecules attack amide-amide hydrogen bonds and break up secondary structure, a disulfide bond stabilizes secondary structure in its vicinity. For example, researchers have identified several pairs of peptides that are unstructured in isolation, but adopt stable secondary and tertiary structure upon forming a disulfide bond between them. Ontology1271664172453:EC50 Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. EC50 [A]50 EC(50) EC(50 The molar concentration of an agonist that produces 50% of the maximal possible effect of that agonist. Other percentage values (EC20, EC40, etc.) can be specified. The action of the agonist may be stimulatory or inhibitory. Ontology1271664172453:ED50 Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. ED50 Either the dose of a drug that produces, on average, a specified all-ornone response in 50% of a test population or, if the response is graded, the dose that produces 50% of the maximal response to that drug. Ontology1271664172453:Electron-electron_repulsion_energy http://www.codessa-pro.com/descriptors/quantum/erepen.htm Electron-electron repulsion energy Electron-electron repulsion energy for a given atomic species Electron-electron repulsion energy for a given atomic species: E(A)=ΣΣΣPμνPλσ< μν| λσ > The first sum in the formula is over B which is not equal to A The second sum in the formula is over μν belonging to A The third sum in the formula is over λσ belonging to B PμνPλσ - density matrix elements over atomic basis {mnls } < μν| λσ > - electron repulsion integrals on atomic basis {mnls } A – given atomic species B – other atoms Ontology1271664172453:Electron_acceptor http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI electron acceptor electron acceptors hydrogen bond acceptor Molecule to which and electron may be transferred from an electron donor. Ontology1271664172453:Electron_donor http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI electron donor electron donors Any molecule that is able to transfer an electron to another chemical species. Ontology1271664172453:Electron_kinetic_energy_density http://www.codessa-pro.com/descriptors/quantum/kinetic.htm Electron kinetic energy density K=-0.25N∫( ψ*▽2ψ+ ψ▽2ψ*)dr' G=∫( ψ*▽2ψ)dr' ψ - wave function N - number of electrons in the molecule ▽ - gradient ▽2ψ - squared gradient of the wave function ψ Ontology1271664172453:Electronic_exchange_energy http://www.codessa-pro.com/descriptors/quantum/eee.htm Electronic exchange energy Electronic exchange energy between two given atoms Electronic exchange energy between two given atoms : E(AB)=ΣΣ PμλPνσ< μλ| νσ > The first sum in the formula is over μλ belonging to A, the second sum is over νσ belonging to B. A – given atomic species B – another atomic species Pmn , Pls, - density matrix elements over atomic basis {mnls } < μλ| νσ > - electron repulsion integrals on atomic basis {mnls } Ontology1271664172453:Electrostatic_Descriptors electrostatic descriptors electrostatic descriptor Descriptor which describes electrostatic interaction. Ontology1271664172453:Electrostatic_balance_parameter http://www.codessa-pro.com/descriptors/electrostatic/ebp.htm Electrostatic balance parameter ν=([σ+]2[σ-]2)/[[σ total]2]2 [σ+]2 variance of positive electrostatic potential in the molecule [σ-]2 variance of negative electrostatic potential in the molecule [σ total]2 total variance of the electrostatic potential in the molecule Ontology1271664172453:Electrostatic_interaction http://dictionary.babylon.com/science/physics/ electrostatic interaction electrostatic interactions electrostatic interaction forces Coulombic interaction Coulombic interactions electrostatic force electrostatic forces 1) Coloumb force: F=k(Q1Q2/r2) (r2-means r square) Q1-charge 1 Q2-charge 2 k-Coulomb constant r2- squared distance between charge Q1 and Q2. 2) Electrostatic potential: V=k(Q1Q2/r) k-Coulomb constant Q1-charge 1 Q2-charge 2 r -distance between charge Q1 and charge Q2 Electrostatic interaction is interaction based on Charles A. de Coulomb law stating that the magnitude of the electrostatic force between two points electric charges is directly proportional to the product of the magnitudes of each charge and inversely proportional to the square of the distance between the charges. Ontology1271664172453:Electrostatic_potential Minkin, V.I., Glossary of terms used in theoretical organic chemistry. Pure Appl. Chem, 1999. 71(10): p. 1919-1981. http://old.iupac.org/reports/1999/7110minkin/e.html electrostatic potential electrostatic potentials A physical property equal in magnitude to the electrostatic energy between the static charge distribution, r(r), of an atomic or molecular system and a positive unit point charge located at r. Ontology1271664172453:Energy_of_protonation http://www.codessa-pro.com/descriptors/quantum/eprot.htm Energy of protonation Energy of protonation: ΔHprot=(EMN+) -EMH -( EH+) EMH – quantum-chemically calculated energy of neutral molecular species EMH+ – quantum-chemically calculated energy of protonated species EH+ – energy of proton in the given reference system Ontology1271664172453:Entity Systems Biology Ontology Version 1.0: http://purl.org/obo/owl/SBO#SBO_0000236 Basic Formal Ontology Version 1.1: http://www.ifomis.org/bfo/1.1#Entity A real being, whether functional or material, that may participate in an interaction, a process or relationship of biological significance. Ontology1271664172453:Enzyme http://history.nih.gov/exhibits/stadtman/glossary.htm http://ucbiotech.org/glossary/index.html enzyme enzymes biocatalysts A complex protein which catalyzes a specific biochemical reaction without changing itself. Enzymes control digestion, muscle contraction, and many other functions of metabolism Protein that facilitates or speeds up certain chemical reactions. Enzymes are used inside of cells to aid in cell growth and reproduction. Enzymes have also been isolated from organisms and used in products like cheese and laundry detergents. Binding sites on enzymes can be active sites or allosteric sites. Ontology1271664172453:Experimental_measures experimental measure experimental measures Ontology1271664172453:FTIR_spectroscopy http://www.eaglabs.com/techniques/analytical_techniques/ftir.php FTIR spectroscopy Fourier Transform Infrared Spectroscopy FTIR Spectroscopy, Fourier Transform Infrared FT-IR spectroscopy Fourier Transform Infrared Spectroscopy (FTIR) provides specific information about chemical bonding and molecular structures, making it useful for analyzing organic materials and certain inorganic materials. Chemical bonds vibrate at characteristic frequencies, and when exposed to infrared radiation, they absorb the radiation at frequencies that match their vibration modes. Measuring the radiation absorption as a function of frequency produces a spectrum that can be used to identify functional groups and compounds. Ontology1271664172453:Flexible_protein-ligand_docking Rarey, M., Protein-Ligand Docking, GMD - German National Research Center for Information Technology, Institute for Algorithms and Scientific Computing (SCAI): 53754 Sankt Augustin, Germany. flexible proteing-ligand docking flexible molecular docking proteing-ligand flexible docking flexible docking flexible ligand docking flexible docking approach flexible docking procedure flexible docking procedures Main assumptions (not valid for simulations) - ligand flexibility is limited to torsion angles (+ ring conformations) - protein is considered as (nearly) rigid - discrete models for conformations and interactions - “binding-pathway” is not considered Application: - Analyzing complexes, searching for possible binding modes - Virtual screening of small molecule databases Ontology1271664172453:Fluorescence_spectroscopy http://bioportal.bioontology.org/visualize/39508 http://www.nature.com/nrm/journal/v6/n3/glossary/nrm1589_glossary.html fluorescence spectroscopy spectroscopy, fluorescence fluorescence correlation spectroscopy FCS Techniques based upon the measurement of the emission of one or more photons by a molecule activated by the absorption of a quantum of electro-magnetic radiation. Typically the emission, which is characterised by a wavelength that is longer than the one of excitatory radiation, occurs within 10-8 seconds. Fluorescence spectroscopy of proteins gives information on the environment of aromatic rings, and can be used in conjunction with external probes to determine the distances between atoms in a molecule. Ontology1271664172453:Force-field_based Wolf, A., State-of-the-art docking and scoring. 2008, Fraunhofer Institute for Algorithms and Scientific Computing SCAI http://www.cs.cmu.edu/~blmt/Seminar/SeminarMaterials/interactions.html force field based force field-based FF FF-based force field based methods force field based function force field energy force field energies 1) Non-bonded terms (van der Waals and electrostatics) of established force-fields like AMBER or Tripos FF. 2) (Lennard Jones or other potentials), problem does not take entropic and solvation effects into account. Example GRID. Ontology1271664172453:Functional_Entity Systems Biology Ontology Version 1.0: http://purl.org/obo/owl/SBO#SBO_0000241 A real thing, defined by its properties or the actions it performs, rather than it physico-chemical structure. Ontology1271664172453:Functional_selectivity Urban, J.D., et al., Functional selectivity and classical concepts of quantitative pharmacology. J Pharmacol Exp Ther, 2007. 320(1): p. 1-13 http://en.wikipedia.org/wiki/Functional_selectivity functional selectivity functional selectivities functionally selective Functional selectivity is the ligand-dependent selectivity for certain signal transduction pathways in one and the same receptor. This can be present when a receptor has several possible signal transduction pathways. To which degree each pathway is activated thus depends on which ligand binds to the receptor. Ontology1271664172453:GI50 http://www.changbioscience.com/stat/ec50.html GI50 BioDataFit is a data fitting program specifically designed for biologists. It can be used to model dose-response, ligand-binding, enzyme kinetics, and growth inhibition. Emphasis is given to the four-parameter model or sigmoidal model, which is frequently used to calculate EC50 (IC50, DC50, or GI50) values in dose-response experiments such as drug screening and inhibition assays. http://www.changbioscience.com/stat/ec50.html The drug concentration giving a 50% reduction in the net protein increase. Ontology1271664172453:Genetic_algorithms MOE: http://www.chemcomp.com/software.htm genetic algorithm genetic algorithms GA genetic programming Genetic algorithms and evolutionary programming evolutionary programming Generic algorithms solve complex optimization problems based on evolutionary principles of natural selection and genetics. The underlying principle is the belief that the new population will be better than the old one. The generic algorithm begins with an initial set of populations that encodes some potential solutions (not optimal). At each step "genetic operators" are used to generate a new and better population by simulating in silico the evolution process. After enough iterations the process is expected to converge to an optimal solution. To be included in a new generation two cases are possible: 1) Natural selection dictated by the scoring function. 2) By being the outcome of the reproduction of the two parents. Those with the highest score are selected to be the parents for the next generation. Ontology1271664172453:Geometric-hashing-based_method Fischer et al, J.Mol.Biol., Vol. 248 (1995), pp. 459 Rarey, M., Protein-Ligand Docking, GMD - German National Research Center for Information Technology, Institute for Algorithms and Scientific Computing (SCAI): 53754 Sankt Augustin, Germany. http://www.cs.cmu.edu/~blmt/Seminar/SeminarMaterials/interactions.html Geometric hashing based method Geometric hashing based methods Geometric hashing Key features: - method from pattern recognition applied to docking Geometric hashing originates from computer vision and was first applied to molecular docking program sby Fischer, Norel Nussinov Wolfson (1993) CPM93, 20-34 and Fischer, Lin, Wolfson and Nussinov (1995) J. Mol. Biology 248, 459-477. Given a picture of a scene and a set of objects within the picture, both represented by points in 2d space, the goal is to recognized some of the models in the scene 1. preprocessing phase: create a hash table from the set of models (for each model, each pair of points define a basis) 2. for each basis, every third point that belongs to the model is expressed in coordinates relative to the basis 3. store a tuple(model, basis) in a has table addressed by teh relative coordinates of the third point (this separate table is necessary, because it is possible that the third point is occluded in the scene). Matching: create a (model,basis) table in the same way as above for the query match to original table advantages: time-efficient deals with partial matching (partially occluded objects( - this is important because usually not all the features of a ligand are in contact with the protein) Specifics: In order to apply geometric hashing to molecular docking, us the sphere representation of DOCK as the underlying model three points to define a axis number of has table entries increases with the 4th power of the number of ligand atoms therefore the basis is described by only two points leaving one degree of freedom open (rotation around the axis defined by the two points). Ontology1271664172453:Geometrical_Descriptors geometrical descriptors geometrical descriptor Descriptor which describes geometrical properties of the molecule. Ontology1271664172453:Gibbs_free_energy http://chemistry.about.com/od/chemistryglossary/g/gibbs-free-energy-definition.htm http://en.wikipedia.org/wiki/Gibbs_free_energy http://encyclopedia2.thefreedictionary.com/Free+energy+change Gibbs free energy Gibbs free energies free energy free energies 1) The Gibbs free energy is defined as: G(p,T) = U + pV − TS which is the same as: G(p,T) = H − TS where: U is the internal energy (SI unit: joule) p is pressure (SI unit: pascal) V is volume (SI unit: m3) T is the temperature (SI unit: kelvin) S is the entropy (SI unit: joule per kelvin) H is the enthalpy (SI unit: joule) 2) The change in free energy for a given process at a particular temperature depends on three factors ΔG=ΔH-TΔS ΔS - entropy change ΔH - enthalpy change A negative value of the enthalpy change indicates a decrease in the heat content of the system and contributes to a favorable value of the free energy; a positive entropy change indicates a decrease in the orderliness of the system and also contributes to a favorable value of the free energy, since a system tends to go from more ordered to less ordered states. It may happen that the change in enthalpy for the reaction is favorable but that of the entropy is unfavorable, or vice versa; in such a case the temperature is the deciding factor since it determines how much weight is given to the entropy change. Enthalpy and Gibbs Free Energy Calculator http://www.shodor.org/unchem/advanced/thermo/thermocalc.html Gibbs free energy is a thermodynamic property that was defined in 1876 by Josiah Willard Gibbs to predict whether a process will occur spontaneously at constant temperature and pressure. Gibbs free energy G is defined as G = H - TS where H, T and S are the enthalpy, temperature, and entropy. Changes in the Gibbs free energy G correspond to changes in free energy for processes at constant temperature and pressure. The change in Gibbs free energy change is the maximum nonexpansion work obtainable under these conditions. ΔG is negative for spontaneous processes, positive for nonspontaneous processes and zero for processes at equilibrium. Ontology1271664172453:Gravitational_index http://www.codessa-pro.com/descriptors/geom/gi.htm Gravitational index Gravitational indexes Gp= Σmimj/(rij)2 Gb= Σmimj/(rij)2 mi, mj - atomic masses of atoms i and j rij - interatomic distance of atoms i and j (rij)2 - interatomic distance of atoms i and j in the power of two Na - number of atoms in the molecule Nb - number of chemical bonds in the molecule In Gp= Σmimj/(rij)2 sum is from i<j till Na In Gb= Σmimj/(rij)2 sim is from i<j till Nb Ontology1271664172453:Hybrid_models http://www.cs.cmu.edu/~blmt/Seminar/SeminarMaterials/interactions.html hybrid model hybrid models hybrid approach hybrid method hybrid methods Fragment-based approaches and genetic algorithms are good for wide coverage of configuration space, but simulation-based methods outperform in finding exact local minimal. Hybrid models have one of each step in it. Ontology1271664172453:Hydrogen_bonding http://pipe.ibibiosolutions.com/Hydrogen%20Bond.html hydrogen bonding H-bonds H-bond hydrogen-bonding interaction hydrogen bond interaction hydrogen bond interactions hydrogen-bonded interaction hydrogen-bonded interactions hydrogen bonds hydrogen bond MarvinSketch is an advanced, Java based chemical editor for drawing chemical structures, queries and reactions. http://www.chemaxon.com/marvin/sketch/index.php In this site go to Tools section after drawing the molecular structure: Other(H bond donor/ Hbond acceptor) Strong intermolecular forces produced by the attraction of a hydrogen atom, already covalently bonded to one electronegative atom, to a second electronegative atom of the same molecule or an adjacent molecule; these bonds are found in compounds containing strong electronegative atoms such as fluorine, oxygen, nitrogen. The energy of a hydrogen bond lies in between the energies of covalent bonds and Vander Waals interactions, and is of the order of 2-10 kcal mol-1. The strength of the hydrogen bond is dependent on the distance between the donor and acceptor atoms, which in turn is dependent on their electronegativities. The standard hydrogen bond between the donor and acceptor atoms is of the order of 2.6Å - 3.5Å, with the optimum at 2.8Å. Distances may be less accurate at low resolution. The highest bonding energy for the hydrogen bond is obtained, when the two negative charges are approximately in line with the positive charge inbetween (O...H-O in water, O...H-N in the oxygen amide hydrogen bond). Deviations from linearity will reduce the bonding energy rapidly. It follows that the "best" hydrogen bond is "close" to linear. Ontology1271664172453:Hydrophobic_interaction http://www.nature.com/nrd/journal/v1/n4/glossary/nrd769_glossary.html http://www.bioportal.gc.ca/English/View.asp?x=696&mid=417 hydrophobic interaction hydrophobic interactions hydrophobic forces hydrophobic force A favourable interaction between nonpolar substructures or surfaces in aqueous solution that is characterized by a large change in heat capacity. An interaction between a hydrophobic ('water-hating') part of a molecule and an aqueous environment. Particularly significant in establishing the conformation of molecules in solution, and thus their biological activity. Many enzymes have a structure where the polypeptide chain is folded to form a hydrophobic core and a hydrophilic ('water-loving') surface. Ontology1271664172453:Hydrophobicity http://www.chem.qmul.ac.uk/iupac/medchem/ah.html#h7 http://antoine.frostburg.edu/chem/senese/101/solutions/glossary.shtml hydrophobicity hydrophobic The association of non-polar groups or molecules in an aqueous environment which arises from the tendency of water to exclude non polar molecules. "water hating" A nonpolar molecule or group that has little affinity for water. Hydrophobic groups on molecules in solution tend to turn in on themselves or clump together with other hydrophobic groups because they are unable to disrupt the network of strong hydrogen bonds in the water around them Ontology1271664172453:IC50 Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. IC50 IC(50) BioDataFit is a data fitting program specifically designed for biologists. It can be used to model dose-response, ligand-binding, enzyme kinetics, and growth inhibition. Emphasis is given to the four-parameter model or sigmoidal model, which is frequently used to calculate EC50 (IC50, DC50, or GI50) values in dose-response experiments such as drug screening and inhibition assays. http://www.changbioscience.com/stat/ec50.html This term is used in a number of ways: (i) the molar concentration of an antagonist that reduces the response to an agonist by 50%; the concentration of agonist should be given; (ii) the molar concentration of an unlabeled agonist or antagonist that inhibits the binding of a radioligand by 50%; the concentration of radioligand should be given; (iii) the molar concentration of an inhibitory agonist that reduces a response by 50% of the maximal inhibition that can be attained; this latter usage is not recommended—instead the term, EC50, should be used since this is an agonist effect. Ontology1271664172453:Incremental_construction MOE:http://www.chemcomp.com/software.htm incremental construction incremental constructions incremental-based method incremental construction algorithm Incremental Construction Algorithms The incremental based approach is another alternative to the fragmentation method instead of docking all small molecule subparts independently in the binding site, it starts with a initial core docked in active site, and new fragments are progressively added and minimized. The treatment is terminated when the entire molecule is formed. Algorithm depends on the choice of the first fragment to be docked. Ontology1271664172453:Independent_Continuant_Entity Basic Formal Ontology Version 1.1: http://www.ifomis.org/bfo/1.1/snap#IndependentContinuant Substantial entity A continuant [snap:Continuant] that is a bearer of quality [snap:Quality] and realizable entity [snap:RealizableEntity] entities, in which other entities inhere and which itself cannot inhere in anything. Ontology1271664172453:Inhibitor http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI C.G Wermuth, et al., Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998). Pure Appl. Chem., 1998. 70(5): p. 1129-1143. inhibitor inhibitors Ligand which competes with substrate for enzyme binding. Molecule inhibiting an interaction by interacting with one or more of its participants. On binding the effector, the catalytic activity of the enzyme towards the substrate may be enhanced, in which case the effector is an activator, or reduced, in which case it is a de-activator or inhibitor. Ontology1271664172453:Insurmountable_antagonism Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. insurmountable antagonism insurmountable antagonist insurmountable antagonists A descriptive term indicating that the maximum effect of the agonist is reduced by either pretreatment or simultaneous treatment with the antagonist. This can encompass several distinct molecular mechanisms such as: (a) irreversible competitive antagonism; (b) noncompetitive antagonism; (c) functional antagonism Ontology1271664172453:Interaction adopted from: http://veritas.adlerplanetarium.org/glossary.shtml interaction interactions molecular interaction molecular interactions protein ligand interactions protein ligand interaction ligand-receptor interactions ligand-receptor interaction receptor-ligand interaction receptor-ligand interactions Interplay of atoms or molecules under the influence a fundamental forces of nature. Ontology1271664172453:Interaction_Descriptor interaction descriptor interaction descriptors descriptor of interaction CDK Descriptor Calculator GUI http://www.rguha.net/code/java/cdkdesc.html E-DRAGON is the electronic remote version of the well known software DRAGON, which is an application for the calculation of molecular descriptors developed by the Milano Chemometrics and QSAR Research Group of Prof. R. Todeschini. These descriptors can be used to evaluate molecular structure-activity or structure-property relationships, as well as for similarity analysis and highthroughput screening of molecule databases. link: http://www.vcclab.org/lab/edragon/start.html Ontology1271664172453:Interaction_type interaction type interaction types type of interaction Ontology1271664172453:Intrinsic_activity http://www.chem.qmul.ac.uk/iupac/medchem/ix.html#i2 http://www.mc.uky.edu/Pharmacology/instruction/pha824mp/PHA824mp.html Buch, D.J.G., FAO in Pharmacology. 2009. Textbook of Receptor Pharmacology, ed. J.C. Foreman and T. Johansen. Vol. 20. 2003, CRC Press intrinsic activity intrinsic activities receptor-mediated intrinsic activity full intrinsic activity Intrinsic activity=(maximum responce to test agonist)/(maximum responce to full agonist acting through the same receptor) Intrinsic activity is the maximal stimulatory response induced by a compound in relation to that of a given reference compound. It is a proportionality factor between tissue response and receptor occupancy.The numerical value of intrinsic activity (alpha) could range from unity (for full agonists, i.e., agonist inducing the tissue maximal response) to zero (for antagonists), the fractional values within this range denoting partial agonists. Intrinsic activity, which is a drug and tissue parameter, cannot be used as a characteristic drug parameter for classification of drugs or drug receptors. For this purpose, a proportionality factor derived by null methods, namely, relative efficacy, should be used. Intrinsic activity is the capacity to generate the responce. Ontology1271664172453:Ion_channel http://www.sci-therapies.info/glossary.htm ion channel ion channels ionic channels ionic channel A protein that serves as a pore in the cell membrane, allowing the regulated flow of ions (e.g., potassium, sodium, and calcium ions) across the membrane and, in turn, neuronal conduction. Protein-based pore in membranes, which induces gradients of ions and thus membrane potentials by selective opening or closing the pore. Ontology1271664172453:Ionic_bonding http://library.thinkquest.org/C005377/content/glossary.htm ionic bonding ionic bond ionic interaction An ionic bond is produced when electrons are transferred from one atom to another. Ontology1271664172453:Isothermal_Titration_Calorimetry protein-protein interaction ontology http://bioportal.bioontology.org/visualize/39508 Isothermal titration calorimetry Isothermal calorimetry ITC Isothermal titration calorimetry (ITC) measures directly the energy associated with a chemical reaction triggered by the mixing of two components. A typical ITC experiment is carried out by the stepwise addition of one of the reactants (~10-6 L per injection) into the reaction cell (~1mL) containing the second reactant. The chemical reaction occurring after each injection either releases or absorbs heat (qi) proportional to the amount of ligand that binds to the protein with a characteristic binding enthalpy (DH). As modern ITC instruments operate on the heat compensation principle, the instrumental response (measured signal) is the amount of power (microcalories per second) necessary to maintain constant the temperature difference between the reaction and the reference cells. Because the amount of uncomplexed protein available progressively decreases after each successive injection, the magnitude of the peaks becomes progressively smaller until complete saturation is achieved. The difference between the concentration of bound ligand in the ith and (i-1)th injections depends on the binding constant Ka and the total ligand injected. The calculations depend on the binding model (number of substrates). Analysis of the data yields DH and DG = -RTlnKa. The entropy change is obtained by using the standard thermodynamic expression DG = DH-TDS. Ontology1271664172453:Kb Oijen, A.v. Binding and kinetics. 2008. Haynie, D.T., Biological Thermodynamics. 2001: Cambridge University Press. Goodrich, J.A. and J.F. Kugel, Binding and Kinetics for Molecular Biologists. 2007: Cold Spring Harbor Laboratory Press. Gilson, M.K., BindingDB: Background. 2009. http://pharmrev.aspetjournals.org/content/55/4/597/T5.expansion Kb KB Kbs K(b) K(B) Kb value Binding (biomolecular reaction):          P+L ⇔ PL Kb - equilibrium binding constant Kb = kbind / kdissociate =[P •L]eq / ([P ]eq [L]eq) [P•L]eq - The equilibrium concentration of protein with bound ligand Kb refers to the equilibrium dissociation constant of a ligand (traditionally, a competitive antagonist) determined by means of a functional assay. Ontology1271664172453:Kd http://seacoast.sunderland.ac.uk/~hs0acu/BIO213/kd.htm http://pharmrev.aspetjournals.org/content/55/4/597/T5.expansion Binding and kinetics Kd Kds K(d K(d) K(D) Kd value KD Another way that people often look at the binding equilibrium is to focus on the dissociation constant, Kd, instead of the binding constant, Kb. The dissociation constant is simply the reciprocal of the binding constant. Kd = 1/ KB= ( [P ]eq [L]eq ) / ( [P •L]eq ) It provides exactly the same information. However, it has a pleasing interpretation: it is the concentration of ligand that gives even odds that a given protein molecule has a ligand bound. That is, for a one-to-one ratio of [P]eq to [P•L]eq, [L]eq = KD. Thus, if one imagines gradually adding more and more ligand and monitoring the increasing fraction of ligand-bound protein, then [L]= KD will be the concentration of ligand for which half the protein is bound. Thus, the lower the value of Kd, the higher the affinity of the ligand. In the drug discovery process, a drug-like ligand with Kd in the millimolar range is considered rather uninteresting; Kd in the low micromolar range might indicate a lead compound (above) worth further chemical optimization; and Kd of low nanomolar or below is good enough for a viable drug candidate. Dissociation Constant (Kd) Calculator http://www.invitrogen.com/site/us/en/home/support/Research-Tools/KD-calculator.html Another way that people often look at the binding equilibrium is to focus on the dissociation constant, Kd, instead of the binding constant, Kb. The dissociation constant is simply the reciprocal of the binding constant. Kd = 1/ KB= ( [P ]eq [L]eq ) / ( [P •L]eq ) It provides exactly the same information. However, it has a pleasing interpretation: it is the concentration of ligand that gives even odds that a given protein molecule has a ligand bound. That is, for a one-to-one ratio of [P]eq to [P•L]eq, [L]eq = KD. Thus, if one imagines gradually adding more and more ligand and monitoring the increasing fraction of ligand-bound protein, then [L]= KD will be the concentration of ligand for which half the protein is bound. Thus, the lower the value of Kd, the higher the affinity of the ligand. In the drug discovery process, a drug-like ligand with Kd in the millimolar range is considered rather uninteresting; Kd in the low micromolar range might indicate a lead compound (above) worth further chemical optimization; and Kd of low nanomolar or below is good enough for a viable drug candidate. It follows that the smaller Kd, the stronger the binding. So 10-6M (or 1mM) indicates weak binding compared to 10-9M (or 1nM). 10-6 means 10 in the pwer of -6 10-9 means 10 in the pwer of -9 Kd refers to the equilibrium dissociation constant of a ligand determined directly in a binding assay using a labeled form of the ligand. Ontology1271664172453:Ki http://pharmrev.aspetjournals.org/content/55/4/597/T5.expansion Rarey, M., Protein-Ligand Docking, GMD - German National Research Center for Information Technology, Institute for Algorithms and Scientific Computing (SCAI): 53754 Sankt Augustin, Germany. Ki K(i)s K(i) K(i Equilibrium Constant: Ki =[PL]/ ([P][L]) [PL] - protein-ligand complex [P] - protein [L] - ligand Ki calculator http://sw16.im.med.umich.edu/software/calc_ki/ Ki refers to the equilibrium dissociation constant of a ligand determined in inhibition studies. The Ki for a given ligand is typically (but not necessarily) determined in a competitive radioligand binding study by measuring the inhibition of the binding of a reference radioligand by the competing ligand of interest under equilibrium conditions. Ontology1271664172453:Kier_and_Hall_valence_connectivity_indices http://www.codessa-pro.com/descriptors/topo/kier-hall.htm Kier and Hall valence connectivity indices Kier and Hall valence connectivity indices: X=ΣΠ(1/δνk)1/2 Ths sum Σ in the formula is from i=1 till Ns The product Π in the formula is from k=1 till m+1 (1/δνk)1/2 means (1/δνk) in the power of 2 δνk=(Zνk-Hk)/(Zk-Zνk-1) Zk - the total number of electrons in the k-th atom Zνk - the number of valence electrons in the k-th atom Hk - the number of hydrogen atoms directly attached to the kth non-hydrogen atom m = 0 - atomic valence connectivity indices m = 1 - one bond path valence connectivity indices m = 2 - two bond fragment valence connectivity indices m = 3 three contiguous bond fragment valence connectivity indices etc. Ontology1271664172453:Kier_flexibility_index http://www.codessa-pro.com/descriptors/topo/kfi.htm Kier flexibility index Φ=( κ1κ2)/Nsa κ1κ2 - Kier shape indicies Nsa - the number of non-hydrogen atom in molecule Ontology1271664172453:Kier_shape_indices http://www.codessa-pro.com/descriptors/topo/ksi.htm Kier shape indices Kier shape indices: 1κ= (Nsa+α)(Nsa+α-1)2(1P+α)2 2κ= (Nsa+α-1)(Nsa+α-2)2(2P+α)2 3κ= (Nsa+α-1)(Nsa+α-3)2(3P+α)2 if Nsa is odd 3κ= (Nsa+α-3)(Nsa+α-2)2(3P+α)2 if Nsa is even nP - the number of paths of the length n in the molecular graph Nsa - the number of non-hydrogen atom in the molecule α=(ri/rci)-1 ri - atomic radius of a given atom rcii - atomic radius of the carbon atom in the sp3 hybridization state Ontology1271664172453:LD50 http://www.wordiq.com/definition/LD50 LD50 In toxicology, the LD50 or colloquially semilethal dose of a particular substance is a measure of how much constitutes a lethal dose. In toxicological studies of substances, one test is to administer varying doses of the substance to populations of test animals; that dose administered which kills half the test population is referred to as the LD50, for "Lethal Dose, 50%" Ontology1271664172453:Lamarckian_genetic_algorithm http://cnx.org/content/m11456/latest/ Lamarckian genetic algorithm LGA A Lamarckian genetic algorithm (LGA): This is the same as the standard genetic algorithm except that, before they are scored, each conformation (gene) is subjected to energy minimization. The next population is then founded by members of this energy-minimized population. The name "Lamarckian" refers to the failed genetic theory of Jean-Baptiste Lamarck, who held that an organism could pass on changed experienced in its lifetime to its offspring. This theory was eventually abandoned in favor of Mendel's now-familiar laws of inheritance. The LGA is faster than both simulated annealing and the standard genetic algorithm, and it allows the docking of ligands with more degrees of freedom. Ontology1271664172453:Ligand Gilson, M. K. & Zhou, H. X. Calculation of protein-ligand binding affinities. Annual Review of Biophysics and Biomolecular Structure 36, 21-42 (2007) http://www.researchherpathways.com/researchherpath/glossary/index.m ligand ligands guest MarvinSketch is an advanced, Java based chemical editor for drawing chemical structures, queries and reactions. http://www.chemaxon.com/marvin/sketch/index.php In this site go to Tools section after drawing the molecular structure: protonation partitioning charge Isomers Geometry (polar surface area, molecular surface area calculation) Conformation analyses (molecular dynamics) Other(H bond donor/ Hbond acceptor) Ligand: organic molecule with molecular weight typically less than 600 Da. A molecule that binds to another molecule; used especially to refer to a small molecule that binds specifically to a larger molecule, eg, an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. To summarise two definitions: Ligand: A small organic molecule with molecular weight typically less than 600 Da that binds specifically to a larger molecule. Ontology1271664172453:Ligand-Based_Pharmacophore ligand-based pharmacophore ligand-based pharmacophores The pharmacophore is determined from a collection of active (and possibly inactive) ligands. No 3D target information is used. Ontology1271664172453:Lipophilicity http://www.chem.qmul.ac.uk/iupac/medchem/ix.html#l5 lipophilicity lipophilic Lipophilicity represents the affinity of a molecule or a moiety for a lipophilic environment. It is commonly measured by its distribution behaviour in a biphasic system, either liquid-liquid (e.g., partition coefficient in octan-1-ol/water) or solid/liquid (retention on reversed-phase high performance liquid chromatography (RP-HPLC) or thin-layer chromatography (TLC) system). "lipid-loving" Ontology1271664172453:Local_polarity_of_molecule http://www.codessa-pro.com/descriptors/electrostatic/lpm.htm Local polarity of molecule П=(1/n)Σl Vi(r)-Vs l l Vi(r)-Vs l- module of Vi(r)-Vs Σ - sum from i to n Vs-average value of the electrostatic potential in the molecule V (r) - electrostatic potential in the molecule n – number of integration points Ontology1271664172453:London_force http://goldbook.iupac.org/L03617.html London force London forces London dispersion forces Attractive forces between apolar molecules, due to their mutual polarizability. They are also components of the forces between polar molecules. Ontology1271664172453:Mass_spectrometry http://www.drugdevelopment-technology.com/glossary/mass-spectrometry.html http://www.nlm.nih.gov/mesh/ mass spectrometry Photometry/Spectrum Analyses, Mass Spectrometry, mass MS Spectrum analyses, Mass mass spectrum analyses mass spectrum mass spectrography Mass Spec ANAL MASS SPECTRUM Mass spectrometry is a method of determining the chemical composition of a substance. The atoms or molecules in a substance are ionised by a beam of high-energy electrons. The ions are focussed by electrostatic and magnetic fields to give a spectrum, which can then be analysed. A mass spectrometry technique used for analysis of nonvolatile compounds such as proteins and macromolecules. The technique involves preparing electrically charged droplets from analyte molecules dissolved in solvent. The electrically charged droplets enter a vacuum chamber where the solvent is evaporated. Evaporation of solvent reduces the droplet size, thereby increasing the coulombic repulsion within the droplet. As the charged droplets get smaller, the excess charge within them causes them to disintegrate and release analyte molecules. The volatilized analyte molecules are then analyzed by mass spectrometry. Ontology1271664172453:Maximum_electrostatic_potential_at_the_molecular_surface http://www.codessa-pro.com/descriptors/electrostatic/mepms.htm Maximum electrostatic potential at the molecular surface Vmax=max[Σ[Za/ l Ra-r l] - ∫p(r')dr'/ l r'-r l ] Za - charge on atomic nucleus a at point Ra p(r') - total electron density of the molecule Ontology1271664172453:Mean_information_content_index http://www.codessa-pro.com/descriptors/topo/mici.htm Mean information content index IC=-Σ((ni/n)*log2(ni/n)) ni - number of atoms in the ith class n - the total number of atoms in the molecule k - number of atomic layers in the coordination sphere around a given atom Σ((ni/n)*log2(ni/n)) - sum is from i=1 till k log2(ni/n)- logarithm of ni/n to base 2 Ontology1271664172453:Metallic_bonding http://www.chemistry-dictionary.com/definition/metallic+bonding.php metallic bonding metallic bond Bonding within metals due to the electrical attraction of positively charges metal ions for mobile electrons that belong to the crystal as a whole. Ontology1271664172453:Minimum_electrostatic_potential_at_the_molecular_surface http://www.codessa-pro.com/descriptors/electrostatic/mep.htm Minimum electrostatic potential at the molecular surface Vmin=min[Σ[Za/ l Ra-r l] - ∫p(r')dr'/ l r'-r l ] Za - charge on atomic nucleus a at point Ra p(r') - total electron density of the molecule Ontology1271664172453:Molecular_Mechanics http://wapedia.mobi/en/Molecular_mechanics molecular mechanics MM MM simulations molecular mechanics simulations Molecular mechanics uses Newtonian mechanics to model molecular systems. The potential energy of all systems in molecular mechanics is calculated using force fields. Molecular mechanics can be used to study small molecules as well as large biological systems or material assemblies with many thousands to millions of atoms. All-atomistic molecular mechanics methods have the following properties: * Each atom is simulated as a single particle. * Each particle is assigned a radius (typically the van der Waals radius), polarizability, and a constant net charge (generally derived from quantum calculations and/or experiment). * Bonded interactions are treated as "springs" with an equilibrium distance equal to the experimental or calculated bond length. Ontology1271664172453:Molecular_dynamics http://www.wordiq.com/definition/Molecular_dynamics molecular dynamics MD simulations MD simulation molecular dynamics simulations molecular dynamics simulation molecular dynamics (MD) simulations molecular dynamics (MD) simulation MD molecular dynamics approach classical MD classical molecular dynamics molecular modeling molecular modeling simulations Molecular dynamics (MD) simulation numerically solves Newton's equations of motion on an atomistic or similar model of a molecular system to obtain information about its time-dependent properties. Ontology1271664172453:Molecular_hyperpolarizability http://www.codessa-pro.com/descriptors/electrostatic/molhyp.htm Molecular hyperpolarizability β - molecular hyperpolarizability μ'=μ + αE +0.5βE2 μ' - perminant dipole moment of the molecule μ - induced dipole moment of the molecule E - external electric field (E2 means that E is in the power of two) Ontology1271664172453:Molecular_polarizability http://www.codessa-pro.com/descriptors/electrostatic/polariz.htm Molecular polarizability α - molecular polarizability μ'=μ + αE +0.5βE2 μ' - perminant dipole moment of the molecule μ - induced dipole moment of the molecule E - external electric field (E2 means that E is in the power of two) Ontology1271664172453:Molecular_surface_area http://www.codessa-pro.com/descriptors/geom/msa.htm Molecular surface area Molecular surface area Sm=ΣSvw -So Svw - van der Waals area of the i-th constituent atom of a molecule So - van der Waals area of atoms inside overlapping atomic envelopes Σ - sum is over i Ontology1271664172453:Molecular_volume http://www.codessa-pro.com/descriptors/geom/mv.htm Molecular volume Molecular volume: Vm=ΣVvw -Vo Vvw - van der Waals volume of the i-th constituent atom of a molecule Vo - volume of overlapping van der Waals atomic envelopes Σ - sum is over i Ontology1271664172453:Monte_Carlo MOE: http://www.chemcomp.com/software.htm Monte Carlo Monte Carlo-based MC Monte Carlo minimization Monte Carlo perturbation Monte-Carlo algorithm Monte Carlo conformational search Monte Carlo method Monte Carlo sampling The Monte Carlo (MC) method provides approximate solutions to avariety of mathematical problems by performing statistical sampling experiments. In each step a random move is applied to the system, following a selection procedure that accepts or rejects the move. The chance of finding the best configuration increases with the number of steps that are made in simulation. Ligand pose modified through bond rotation, translation, new conformation with lower score is kept, a higher score is kept or rejected. Ontology1271664172453:Multiconformer_docking Wolf, A., State-of-the-art docking and scoring. 2008, Fraunhofer Institute for Algorithms and Scientific Computing SCAI. http://www.cs.cmu.edu/~blmt/Seminar/SeminarMaterials/interactions.html multiconformer docking multi-conformer docking multiconf dock Rigid-body docking of multiconformer libraries, often with shape complementarity or interaction site matching algorithms. This method uses the same algorithms as the rigid-body docking algorithms, but apply them to ensembles of rigid structures, each representing a different conformation of the ligand Flexibase/FLOG algorithm: - store a small set of diverse conformations for each molecule from a given database created with distance-geometry methods - select 25 conformations based on dissimilarity criteria (RMSD) Lorber and Shoichet approach: - generate 300 conformations per molecule, and define one rigid part of the molecule and superimpose - faster than independent docking Ontology1271664172453:NMR http://www.nlm.nih.gov/mesh/ protein-protein interaction ontology http://bioportal.bioontology.org/visualize/39508 NMR Magnetic Resonance Magnetic Resonance Spectroscopy MR Spectroscopy NMR Spectroscopy Spectroscopy, NMR Nuclear Magnetic Resonance nmr Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). NMR requires a small volume of concentrated protein solution that is placed in a strong magnetic field. Certain atomic nuclei, and in particular hydrogen, have a magnetic moment or spin; that is, they have an intrinsic magnetisation, like a bar magnet. The spin aligns along the strong magnetic field, but can be changed to a misaligned excited state in response to applied radio frequency (RF) pulses of electromagnetic radiation. When the excited hydrogen nuclei relax to their aligned state, they emit RF radiation, which can be measured and displayed as a spectrum. The nature of the emitted radiation depends on the environment of each hydrogen nucleus, and if one nucleus is excited, it will influence the absorption and emission of radiation by other nuclei that lie close to it. It is consequently possible, by an ingenious elaboration of the basic NMR technique known as two-dimensional NMR, to distinguish the signals from hydrogen nuclei in different amino acid residues and to identify and measure the small shifts in these signals that occur when these hydrogen nuclei lie close enough to interact: the size of such a shift reveals the distance between the interacting pair of hydrogen atoms. In this way NMR can give information about the distances between the parts of the protein molecule. NMR provides information about interacting atoms thereby permitting to obtain information about protein structure. Ontology1271664172453:Negative_allosteric_modulation http://en.wikipedia.org/wiki/Allosteric_regulation negative allosteric modulation allosteric inhibition Negative allosteric modulation (also known as allosteric inhibition) occurs when the binding of one ligand decreases the affinity for substrate at other active sites. Ontology1271664172453:Newton-Raphson_method http://chsfpc5.chem.ncsu.edu/~franzen/CH795N/lecture/IV/IV.html Steinbach, P.J., Two-dimensional distributions of activation enthalpy and entropy from kinetics by the maximum entropy method. Biophys J, 1996. 70(3): p. 1521-8. Newton-Raphson method Newton-Raphson optimization algorithm Second derivative method. The Newton-Raphson method uses the second derivatives as well as the first derivatives. In addition to using the gradient information, Newton-Raphson uses the curvature to predict where along the gradient the function will change direction. Storing and manipulating the second derivative matrix is prohibitive for large systems. Ontology1271664172453:Non_bonded_interaction http://cmt.dur.ac.uk/sjc/thesis_dlc/node75.html non-bonded interaction non-bonded interactions non-covalent interactions non-covalent interaction NB nonbonded interaction noncovalent interaction noncovalent interactions Non-bonded interactions are interactions between atoms which are not linked by covalent bonds. Non-bonded interactions act between atoms in the same molecule and those in other molecules. Ontology1271664172453:Noncompetitive_antagonism Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. noncompetitive antagonism Agonist and antagonist can be bound to the receptor simultaneously; antagonist binding reduces or prevents the action of the agonist with or without any effect on the binding of the agonist. Ontology1271664172453:Normal_coordinate_EigenValues http://www.codessa-pro.com/descriptors/thermodynamic/index.htm http://www.codessa-pro.com/descriptors/thermodynamic/eva.htm EVA Normal coordinate EigenValues Normal coordinate EigenValues (EVA): EVAx=Σ((1/(σ√(2π)))*exp[-(x-νi)2/2σ2]) In this formula sum is started from i=1 till 3N-6 In exp[-(x-νi)2/2σ2], (x-νi)2 means (x-νi) is in the power of 2 and σ2 means σ is in the power of two. νi - frequencies of normal vibrations in the molecule x - sampling point on frequency scale σ - fixed standard deviation for all Gaussian functions characterizing the shape of the vibrational peak Ontology1271664172453:Nuclear-electron_attraction_energy http://www.codessa-pro.com/descriptors/quantum/neae.htm Nuclear-electron attraction energy Nuclear-electron attraction energy between two given atoms Nuclear-electron attraction energy for a given atomic species: Ene(A)=ΣΣ Pμν< μ | Zb/Rib | ν > The first sum in the formula is over b and the second summ is is over μν belonging to A. < μ | Zb/Rib | ν > - electron-nuclear attraction integrals on atomic basis {mn} Pμν - density matrix elements over atomic basis {mn} Zb - charge of atomic nucleus, b Rib - distance between the electron and atomic nucleus, b A - given atomic species b - other atoms Ontology1271664172453:Nuclear_repulsion_energy http://www.codessa-pro.com/descriptors/quantum/nre.htm Nuclear repulsion energy Nuclear repulsion energy between two given atoms Nuclear repulsion energy between two given atoms: Enn(AB)=(ZaZb)/Rab A – given atomic species B – another atomic species ZA - charge of atomic nucleus, A ZB - charge of atomic nucleus, B RiB - distance between the atomic nuclei, A and B Ontology1271664172453:Occurrent_Entity Basic Formal Ontology Version 1.1: http://www.ifomis.org/bfo/1.1/span#Occurrent Perdurant An entity [bfo:Entity] that has temporal parts and that happens, unfolds or develops through time. Sometimes also called perdurants. Ontology1271664172453:PIC50 http://en.wikipedia.org/wiki/IC50 PIC50 PIC(50) half maximal inhibitory concentration - (IC50) If IIC50 is converted to the pIC50 scale (-log IC50), in which higher values indicate exponentially greater potency. Ontology1271664172453:Pharmacophore C.G Wermuth, et al., Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998). Pure Appl. Chem., 1998. 70(5): p. 1129-1143. http://www.chem.qmul.ac.uk/iupac/medchem/ix.html#p7 Taboureau, O., 3D descriptors and fingerprints, Chemoinformatics, CBS-BioCentrum. Pharmacophore Pharmacophores Pharmacophoric element Pharmacophoric elements ph4 3D-pharmacophore 3D-pharmacophore model Pharmacophore model Pharmacophore models An ensemble of steric and electronic features that are necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger (or block) its biological response. A pharmacophore does not represent a real molecule or a real association of functional groups, but a purely abstract concept that accounts for the common molecular interaction capacities of a group of compounds towards their target structure. The pharmacophore can be considered as the largest common denominator shared by a set of active molecules. Pharmacophoric points do not necessarily coincide with the positions of individual atoms Ontology1271664172453:Polar_Surface_Area http://en.wikipedia.org/wiki/Polar_surface_area polar surface area polar surface areas PSA The polar surface area (PSA) is defined as the surface sum over all polar atoms, (usually oxygen and nitrogen), including also attached hydrogens Ontology1271664172453:Polarity_parameter http://www.codessa-pro.com/descriptors/electrostatic/polarity.htm Polarity parameter Polarity parameters Polarity parameters: P=Qmax-Qmin P'=(Qmax-Qmin)/R P''=(Qmax-Qmin)/R2 Qmax - the most positive atomic partial charge in the molecule Qmin - the most negative atomic partial charge in the molecule R - distance between the most positive and the most negative atomic partiak charges in the molecule R2 means that R is in the power of 2 Ontology1271664172453:Pose http://wapedia.mobi/en/Docking_%28molecular%29 pose poses docking pose docking poses ligand-binding pose protein-ligand docking pose ligand pose binding pose docked pose docked poses the lowest energy pose experimental pose native pose crystallographic spose Candidate pose native-like poses docked binding mode docked ligand pose docked ligand poses docking mode docking modes A candidate binding mode. Ontology1271664172453:Pose_clustering http://www.cs.cmu.edu/~blmt/Seminar/SeminarMaterials/interactions.html pose clustering clustered conformations pose clustering approach pose clustering methods clustering of all poses originally developed to detect objects in pictures with an unknown camera location algorithm matches each triangle of object points in the two pictures from a match, calculate the position of the camera, and store the locations and cluster them identify large clusters LUDI model is used as underlying model of molecular interactions interaction points are approximated by discrete points. Ontology1271664172453:Positive_allosteric_modulation_ http://en.wikipedia.org/wiki/Allosteric_regulation Positive allosteric modulator Positive allosteric modulators positive allosteric modulation allosteric activation Positive allosteric modulation (also known as allosteric activation) occurs when the binding of one ligand enhances the attraction between substrate molecules and other binding sites. Ontology1271664172453:Positive_allosteric_modulator http://en.wikipedia.org/wiki/Positive_allosteric_modulator PAM positive allosteric modulator positive allosteric modulators A positive allosteric modulator (PAM) is a drug which increases the activity of a receptor indirectly via activation of an allosteric site on the protein. PAMs are similar to agonists in that they contribute to overall receptor activation, but they are different due to the fact that they do so in a functionally distinctive way. Ontology1271664172453:Potency Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. potency potencies drug potency chemical potency inhibitory potency inhibition potency binding potency functional potency ligand potency steady-state potency competitive potency biological potency An expression of the activity of a drug, in terms of the concentration or amount needed to produce a defined effect; an imprecise term that should always be further defined ( EC50, IC50, etc.). Ontology1271664172453:Principal_moments_of_inertia_of_a_molecule http://www.codessa-pro.com/descriptors/geom/pm.htm Principal moments of inertia of a molecule Principal moments of inertia of a molecule: Ik=Σ(mi)(rik)2 mi - atomic weights of constituent atoms of a molecule rik - distance of the i-th atomic nucleus from the k-th main rotational axes (k = X, Y or Z) (rik)2 is rik in the power of two Σ(mi)(rik)2 sum is over i Ontology1271664172453:Processual_Entity Basic Formal Ontology Version 1.1: http://www.ifomis.org/bfo/1.1/span#ProcessualEntity An occurrent [span:Occurrent] that exists in time by occurring or happening, has temporal parts and always involves and depends on some entity. Ontology1271664172453:Protein_biological_unit http://www.proteopedia.org/wiki/index.php/Biological_Unit Xie, L., et al., Knowledge Discovery of Protein-Ligand Interaction Network, in Conference on Semantics in Healthcare and Life Sciences (CSHALS). 2010: Cambridge/Boston, MA. protein biological unit protein biological units The Biological Unit is the quaternary structure of a protein that is believed to be the functional form of the molecule. Ontology1271664172453:Protein_domain http://www.nlm.nih.gov/research/umls/ http://en.wikipedia.org/wiki/Protein_domain Xie, L., et al., Knowledge Discovery of Protein-Ligand Interaction Network, in Conference on Semantics in Healthcare and Life Sciences (CSHALS). 2010: Cambridge/Boston, MA. protein domain protein domains protein motif protein region signatures signature domain domains protein feature motif ligand-binding domain ligand-binding domains LBD protein domain protein domains protein motif protein region signatures signature domain domains protein feature motif motifs ligand-binding domain ligand-binding domains A structurally or functionally defined protein region. A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural domains. One domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. Domains vary in length from between about 25 amino acids up to 500 amino acids in length. Ontology1271664172453:Protein_fragment http://www.nlm.nih.gov/research/umls/ Xie, L., et al., Knowledge Discovery of Protein-Ligand Interaction Network, in Conference on Semantics in Healthcare and Life Sciences (CSHALS). 2010: Cambridge/Boston, MA. protein fragment protein fragments A fragment of a protein, which may be a diagnostic or prognostic factor and used as a biomarker. Ontology1271664172453:Protein_functional_site http://elm.eu.org/help.html Xie, L., et al., Knowledge Discovery of Protein-Ligand Interaction Network, in Conference on Semantics in Healthcare and Life Sciences (CSHALS). 2010: Cambridge/Boston, MA. protein functional site protein functional sites functional site functional sites Protein functional site is a set of short linear (sub)sequences that can be related to molecular function. A primary prerequisite for a site to be functional is that it must be recognised by the protein that will act upon it, in other words it must occur in the proper biochemical context. This implies that the functional site must reside in a non-structured region of a protein; either in non-globular region or in loops whithin globular domains.Furthermore, in order for a molecular function to occur, the functional site must be in the right cellular context. That is, the protein harbouring the functional site must be in the right cellular compartment. Finally, while some functional sites are found in all eukaryotes, others are restricted to a specific species range. Ontology1271664172453:QSPR QSPR QSPR model QSPR models Ontology1271664172453:Quantitative_Structure-Activity_Relationships http://www.chem.qmul.ac.uk/iupac/medchem/ix.html#q2 quantitative structure-activity relationship quantitative structure-activity relationships QSAR quantitative structure-activity relationship approach quantitative structure-activity relationship Quantitative structure-activity relationships are mathematical relationships linking chemical structure and pharmacological activity in a quantitative manner for a series of compounds. Methods which can be used in QSAR include various regression and pattern recognition techniques Ontology1271664172453:Quantitative_Structure_Pharmacokinetic_Relationships http://www.pharmabiz.com/article/detnews.asp?articleid=11415&sectionid=46 Quantitative structure pharmokinetic relationship Quantitative structure pharmokinetic relationships QSPKR The extension of the idea and principles of QSAR to the pharmacokinetic data has led to emergence of new tool called Quantitative Structure Pharmacokinetic Relationship studies (QSPR studies). QSPR studies can be suitably utilized at the early stage of clinical trials to be design a better molecule with favourable biological activity and pharmacokinetic character. There is a renewed interest to use the pharmacokinetic data to design an optimum molecule from the point of therapeutic efficacy, reduced toxicity, quick absorption duration, of action, etc. The QSPR studies have become an integral part of rational drug design and formulation development. The optimum characterization of ADME characters of a molecule can be manipulated by addition/substitution or deletion of certain chemical features or groups to the molecule without interfering with its pharmacodynamic interaction. There are studies of QSPR on variety of therapeutic categories including barbiturates, sulfomnamides, carbamates, basic drugs, acidic drug etc. for their absorption, distribution, metabolism, elimination, which has led to understand that it is possible to manipulate the PK parameters without muddling with the therapeutic effects. Ontology1271664172453:Quantitative_Structure_Property_Relationships http://www.drugdesign.com/web/teaching/glossary Quantitative structure property relationship Quantitative structure property relationships Quantitative Structure Property Relationships, QSPR - QSPR is an extension of QSAR and tries to formulate the relationship between structure and any molecular property in terms of a mathematical model. Ontology1271664172453:Quantum_Chemical_Descriptors Quantum Chemical Descriptors Quantum Chemical Descriptor descriptor which describe quantum chemical properties. Ontology1271664172453:Quantum_dynamics "Complex Quantum Dynamics and Mesoscopic Phenomena Group". Department of Physics, Wesleyan University. Retrieved 2010-01-25. Joan Vaccaro (2008-06-26). "Centre for Quantum Dynamics, Griffith University". Quantiki. Retrieved 2010-01-25. Teufel, S., Adiabatic Perturbation Theory in Quantum Dynamics, Habilitationsschrift. Lecture Notes in Mathematics, 2003. 1821. Quantum Dynamics QD QM simulations Quantum dynamics is the study of the dynamics of mesoscopic objects, objects who are neither macroscopic, nor microscopic, and so cannot be accurately described by either classical dynamics or quantum mechanics. Quantum dynamics also lies at the interface between theoretical and experimental physics; it is relevant for burgeoning fields, such as quantum computing and atomic optics. In mathematics, quantum dynamics is the study of the mathematics behind quantum mechanics.Specifically, as a study of dynamics, this field investigates how quantum mechanical observables change over time. Most fundamentally, this involves the study of one-parameter automorphisms of the algebra of all bounded operators on the Hilbert space of observables (which are self-adjoint operators). Ontology1271664172453:RMSD http://openwetware.org/wiki/Wikiomics:RMSD RMSD Root Mean Square Deviation Normally a rigid superposition which minimizes the RMSD is performed, and this minimum is returned. Given two sets of n points V and W, the RMSD is defined as follows: RMSD(V,W)=√( (1/n)∑||Viy-Wiy||2 ) = √(1/n)∑( (Vix-Wix)2+(Viy-Wiy)2+(Viz-Wiz)2 ) Sum ∑ in this formula is from i=1 till n. ||Viy-Wiy||2 means ||Viy-Wiy|| in the power of two (Vix-Wix)2 means (Vix-Wix) in the power of two (Viy-Wiy)2 means (Viy-Wiy) in the power of two (Viz-Wiz)2 means (Viz-Wiz) in the power of two RMSD means Root Mean Square Deviation. It is often used in 3D geometry of molecules to compare two conformations of a given set of points, typically atoms. In other words, given a list of paired points, it gives a measure of the distance between these points. Ontology1271664172453:Raman_spectroscopy http://www.nlm.nih.gov/mesh/ Raman Spectroscopy Spectroscopy, Raman Spectroscopy, IR/UV/Raman Raman Spectrum Analysis Raman spectrum anal FT-Raman Spectroscopy FT-IR Raman Spectroscopy FT-Raman Spectroscopy Raman spectroscopy is a spectroscopic technique based on inelastic scattering of monochromatic light, usually from a laser source. Inelastic scattering means that the frequency of photons in monochromatic light changes upon interaction with a sample. Photons of the laser light are absorbed by the sample and then reemitted. Frequency of the reemitted photons is shifted up or down in comparison with original monochromatic frequency, which is called the Raman effect. This shift provides information about vibrational, rotational and other low frequency transitions in molecules. Analysis of the intensity of Raman scattering of monochromatic light as a function of frequency of the scattered light.;A plot of the difference in intensities between Raman scattered light using right and left circularly polarized incident lig Ontology1271664172453:Ranking http://wapedia.mobi/en/Docking_%28molecular%29 ranking rank ranked The process of classifying which ligands are most likely to interact favorably to a particular receptor based on the predicted free-energy of binding. Ontology1271664172453:Receptor http://goldbook.iupac.org/RT06978.html receptor receptors receptor protein receptor proteins A receptor is a protein or a protein complex in or on a cell that specifically recognizes and binds to a compound acting as a molecular messenger (neurotransmitter, hormone, lymphokine, lectin, drug, etc). In a broader sense, the term receptor is often used as a synonym for any specific (as opposed to non-specific such as binding to plasma proteins) drug binding site, also including nucleic acids such as DNA. Ontology1271664172453:Relative_shadow_areas_of_a_molecule http://www.codessa-pro.com/descriptors/geom/rsam.htm Relative shadow areas of a molecule Relative shadow areas of a molecule Sk=(∮(νdρ-ρdν))/S ∮ integral is over C S=X*Y, X*Z or Y*Z C – contour of the projection of the molecule on the plane defined by two principal axes of the molecule (k = XY, XZ or YZ plane) ν - x or y ρ - y or z Ontology1271664172453:Resonance_energy http://www.codessa-pro.com/descriptors/quantum/reb.htm Resonance energy Resonance energy between given two atomic species Resonance energy between given two atomic species: Er(AB)=ΣΣ(Pμν)(βμν) first sum is over μ belong to A second sum is over ν belong to B A – given atomic species B – another atomic species Pμν - density matrix elements over atomic basis {μν} βμν - resonance integrals on atomic basis {μν} Ontology1271664172453:Rigid-body_protein-ligand_docking Rarey, M., Protein-Ligand Docking, GMD - German National Research Center for Information Technology, Institute for Algorithms and Scientific Computing (SCAI): 53754 Sankt Augustin, Germany. rigid-body proteing-ligand docking rigid-body docking algorithm rigid-body docking approach rigid-body docking rigid docking Main assumptions: - protein is considered as rigid - ligand is considered as rigid Applications: - docking of small or very rigid molecules - docking of fragments (flexible docking, de novo design, combinatorial library design) - docking of multi-conformer databases Ontology1271664172453:Saddle_surface http://en.wikipedia.org/wiki/Saddle_surface saddle surface saddle surfaces A saddle surface is a smooth surface containing one or more saddle points. The term derives from the peculiar shape of historical horse saddles, which curve both up and down. Classical examples of two-dimensional saddle surfaces in the Euclidean space are second order surfaces, the hyperbolic paraboloid z = x2 − y2 (which is often referred to as the saddle surface or "the standard saddle surface") and hyperboloid of one sheet. x2 −means x is in the power of 2 y2- means y is in the power of 2 Ontology1271664172453:Shadow_area http://www.codessa-pro.com/descriptors/geom/sam.htm Shadow area Shadow areas of a molecule Shadow areas of a molecule Sk=0.5∮(νdρ-ρdν) ∮ integral is over C C – contour of the projection of the molecule on the plane defined by two principal axes of the molecule (k = XY, XZ or YZ) ν - x or y ρ - y or z Ontology1271664172453:Shape_and_Chemical_Complementary_Score Chemoinformatics and Medicinal Chemistry Group Departamento de Química – UFMG http://www.nequim.qui.ufmg.br jlopes@netuno.lcc.ufmg.br shape and chemical complementarity score shape and chemical complementarity scores Divide accessible protein surface into zones:Hydrophobic, Hydrogen-bond donating, Hydrogen-bond accepting Do the same for the ligand surface. Find ligand orientation with best complementarity score. Ontology1271664172453:Silent_antagonist http://en.wikipedia.org/wiki/Receptor_antagonist#Silent_antagonists silent antagonist silent antagonists Silent antagonists are competitive receptor antagonists that have zero intrinsic activity for activating a receptor. They are true antagonists, so to speak. The term was created to distinguish fully inactive antagonists from weak partial agonists or inverse agonists. Ontology1271664172453:Solvation_energy Minkin, V.I., Glossary of terms used in theoretical organic chemistry. Pure Appl. Chem, 1999. 71(10): p. 1919-1981. Leach, A., Molecular Modelling: Principles and Applications. 2001: Prentice Hall. solvation energy energy of solvation solvation ΔGsol=ΔG(electrostatic)+ΔG(Vam der Waals)+ΔG(free energy required to form solute cavity within the solvent) The change in Gibbs energy when an ion or molecule is transferred from a vacuum (or the gas phase) to a solvent. The main contributions to the solvation energy come from: a) the cavitation energy of formation of the hole which preserves the dissolved species in the solvent; b) the orientation energy of partial orientation of the dipoles; c) the isotropic interaction energy of electrostatic and dispersion origin; d) the anisotropic energy of specific interactions, e.g. hydrogen bonds, donor-acceptor interactions etc. Ontology1271664172453:Solvent-accessible_molecular_surface_area http://www.codessa-pro.com/descriptors/geom/solvent.htm Solvent-accessible molecular surface area Ssa=(A+) + As+ (A-) A+ convex areas of a molecule As saddle areas of a molecule A- concave areas of a molecule Ontology1271664172453:Solvent-excluded_molecular_volume http://www.codessa-pro.com/descriptors/geom/semv.htm Solvent-excluded molecular volume Solvent-excluded molecular volume: Vmol(SE)=Vp+Σ(V+)+ΣVs+Σ(V-)+Vac+Vnc Vp - volume of internal polyhedron Σ(V+) - volume pieces between the center of an atom and the convex face of the solvent-accessible surface ΣVs - volume of saddle pieces Σ(V-) - volume of concave pieces Vac, Vnc - cusp volume pieces Ontology1271664172453:Specificity specificity specificities substrate specificity receptor specificity molecular specificity binding specificity binding specificities drug specificity target specificity ligand-receptor specificity domain specificity recognition specificity Ontology1271664172453:Stacking_interaction http://www.jbc.org/content/273/25/15458.full stacking interaction stacking interactions ring stacking interaction parallel ring stacking interaction hydrophobic stacking interactions Base-Stacking Interactions Attractive nonbonded interactions between aromatic rings. Ontology1271664172453:Standard_heat_of_formation http://www.codessa-pro.com/descriptors/quantum/shf.htm Standard heat of formation Standard heat of formation: ΔHf=Hf-ΣHaf Hf - quantum-chemically calculated total energy of the molecule Haf - quantum-chemically calculated energies of isolated atoms, a Ontology1271664172453:Steepest_descent http://mathworld.wolfram.com/MethodofSteepestDescent.html http://www.boomer.org/c/p3/c11/c1104.html http://linneus20.ethz.ch:8080/3_6.html steepest descent SD First-order minimization method. Steepest Descent (SD) computes the direction of steepest descent and for that it requires the gradient. Hence it requires that we compute n derivatives.Since we compute the function and n derivatives we have to do n+1 computations. Steepest Descent: an algorithm for finding the nearest local minimum of a function which presupposes that the gradient of the function can be computed. The method of steepest descent, also called the gradient descent method, starts at a point P(0) and, as many times as needed, moves from P(i) to P(i+1) by minimizing along the line extending from P(i) in the direction of minus fradient of f(P(i)) ( -grad (f(P(i)) ), the local downhill gradient. Advantages of this method Always 'downhill' Avoids 'saddle points' Efficient further from the minimum Disadvantages of this method Slower close to minimum Linear search may cause problems Might 'zigzag' down valleys Ontology1271664172453:Structural_information_content_index http://www.codessa-pro.com/descriptors/topo/sici.htm IC=-Σ((ni/n)*log2(ni/n)) SIC=IC/log2(ni/n) structural information content index ni - number of atoms in the ith class n - the total number of atoms in the molecule k - number of atomic layers in the coordination sphere around a given atom Σ((ni/n)*log2(ni/n)) - sum is from i=1 till k log2(ni/n)- logarithm of ni/n to base 2 Ontology1271664172453:Structure-Activity_Relationship Structure activity relationship Structure activity relationships SAR SARs SAR model SAR models Structure activity relationship models The relation between the chemical structure of a compound and its biological or pharmacological activity. Ontology1271664172453:Surface_curvature surface curvature Ontology1271664172453:Syntopic_interaction Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. syntopic interaction syntopic interactions An interaction between ligands that bind to the same recognition site, or to recognition sites that overlap, on the receptor macromolecule.The term syntopic should be confined to defining interactions at a common site and should not be used interchangeably with the term orthosteric. This term is most commonly associated with the description of competitive interactions between ligands that bind to the primary (orthosteric) site on a receptor, but need not be restricted to this specific situation. A syntopic interaction can also occur between different ligands that share a similar recognition domain (e.g., a common allosteric site) anywhere on the receptor macromolecule. Ontology1271664172453:Tabu_search MOE: http://www.chemcomp.com/software.htm Stepanenko, S. and B. Engels, Tabu search based strategies for conformational search. J Phys Chem A, 2009. 113(43): p. 11699-705. Tabu search TS Tabu based strategy Tabu-like search Tabu search based strategy Tabu search based strategies Tabu search is a stochastic search algorithm that maintains a list of previously visited poses. These poses are forbidden and can not be revisited (they are "taboo"). TS effectively guides the search process into unvisited areas of the space and has been successfully implemented in a number of docking programs. Tabu search is based on neighborhood search, which means that at each step the algorithm considers the set of all possible neighborhood states and chooses the best one even through it might be worse than the current move. The best new solution (not in the Tabu list) is then chosen as the new current solution and the same process is repeated again. Not re-visiting previously visited states helps in two ways: 1) Avoiding being trapped in local minima. 2) Better exploration of the space. Summary: Search is prevented from revisiting already explored areas of conformational space. Ontology1271664172453:Target-Based_Pharmacophore target-based pharmacophore target-based pharmacophores target based pharmacophore model The pharmacophore is derived based on knowledge of the 3D receptor structure only. Ontology1271664172453:The_CLIX_approach Lawrence et al, PROTEINS: Struct., Func., and Gen., Vol. 12 (1992), pp 31 Rarey, M., Protein-Ligand Docking, GMD - German National Research Center for Information Technology, Institute for Algorithms and Scientific Computing (SCAI): 53754 Sankt Augustin, Germany. The CLIX approach CLIX approach Based on interaction maps calculated with GRID. Algorithm: - identification of interaction target points in the maps - enumeration of all pairs of distance-compatible matches - superposition of two matches groups, sampling of rotation around common axis: - searching for additional matches - overlap test, scoring Ontology1271664172453:Thermodynamic_Descriptors http://www.codessa-pro.com/descriptors/thermodynamic/index.htm Thermodynamic Descriptors Thermodynamic Descriptor Descriptor which describes thermodynamic properties of the molecule. Ontology1271664172453:Thermodynamics_of_protein-ligand_interactions thermodynamics of protein-ligand interaction thermodynamics of protein-ligand interactions Ontology1271664172453:Topological_Descriptors Gonzalez-Diaz, H., et al., Medicinal chemistry and bioinformatics--current trends in drugs discovery with networks topological indices. Curr Top Med Chem, 2007. 7(10): p. 1015-29. Gonzalez-Diaz, H., et al., Proteomics, networks and connectivity indices. Proteomics, 2008. 8(4): p. 750-78. Topological Descriptors Topological Descriptor Topological descriptors are derived from hydrogen-suppressed molecular graphs, in which the atoms are represented by vertices and the bonds by edges. The connections between the atoms can be described by various types of topological matrices (e.g., distance or adjacency matrices), which can be mathematically manipulated so as to derive a single number, usually known as graph invariant, graph-theoretical index or topological index. Ontology1271664172453:Topological_electronic_indices http://www.codessa-pro.com/descriptors/topo/tei.htm Topological electronic indices Topological electronic indices T1 and T2 T1=Σ|qi-qj |/(rij)2 T2 = Σ|qi-qj|/(rij)2 qi- partial charge on the i-th atom rij - distance between i-th and j-th atoms (rij)2 - rij in the power of two Nsa - number of non-hydrogen atom in the molecule Nb - number of bonds between non-hydrogen atom in the molecule In T1=Σ(qi-qj)/(rij)2 , Σ(qi-qj) sum is fron i<j till Nsa In T2 = Σ|qi-qj|/(rij)2, sum is fron i<j till Nb Ontology1271664172453:Total_electronic_energy_ http://www.codessa-pro.com/descriptors/quantum/teem.htm Total electronic energy Total electronic energy of the molecule Total electronic energy of the molecule: Eel= 2Tr(RF) - Tr(RG) R - first order density matrix F - matrix representation of the Hartree-Fock operator G - matrix representation of the electron repulsion energy Ontology1271664172453:Total_electrostatic_interaction_energy http://www.codessa-pro.com/descriptors/quantum/eie.htm Total electrostatic interaction energy Total electrostatic interaction energy between two given atomic species Total electrostatic interaction energy between two given atomic species: Ec(AB)=Eee(AB)+Ene(AB)+Enn(AB) A – given atomic species B – another atomic species Eee(AB)- electronic repulsion energy between two atomic species Ene(AB)- electron-nuclear attraction energy between two atomic species Enn(AB)- nuclear repulsion energy between two atomic species Ontology1271664172453:Total_energy_ http://www.codessa-pro.com/descriptors/quantum/tem.htm Total energy Total energy of the molecule Total energy of the molecule: Etot=Eel + Σ(ZaZb)/Rab Eel - total electronic energy of the molecule Za, Zb - nuclear charges of atoms A and B Rab - distance between nuclei A and B Ontology1271664172453:Total_interaction_energy http://www.codessa-pro.com/descriptors/quantum/tie.htm Total interaction energy Total interaction energy between two given two atomic species Total interaction energy between two given two atomic species: Etot(AB)=Ec(AB)+Eexe(AB) A – given atomic species B – another atomic species Ec(AB)- electrostatic interaction energy between two atomic species Eexc(AB)- electronic exchange energy between two atomic species Ontology1271664172453:Total_intramolecular_electrostatic_interaction_energy http://www.codessa-pro.com/descriptors/quantum/ieie.htm Total intramolecular electrostatic interaction energy Total intramolecular electrostatic interaction energy: Ec(tot)= 0.5ΣEc(A) A - given atomic species EC(A) - electrostatic energy for atom A ΣEc(A) - sum is over A Ontology1271664172453:Total_molecular_one-center_electron-electron_repulsion_energy http://www.codessa-pro.com/descriptors/quantum/ere.htm Total molecular one-center electron-electron repulsion energy Total molecular one-center electron-electron repulsion energy Eee(tot)=ΣEee(A) A - given atomic species Eee(A) - electron-electron repulsion energy for atom A ΣEee(A) - sum is over A Ontology1271664172453:Total_molecular_one-center_electron-nuclear_attraction_energy http://www.codessa-pro.com/descriptors/quantum/enae.htm Total molecular one-center electron-nuclear attraction energy Total molecular one-center electron-nuclear attraction energy: Ene(tot)=ΣEne(A) A – given atomic species Ene(A) - electron-nuclear attraction energy for atom A ΣEne(A) - sum is over A Ontology1271664172453:Total_variance_of_the_surface_electrostatic_potential http://www.codessa-pro.com/descriptors/electrostatic/tvs.htm Total variance of the surface electrostatic potential (σ tot)2= 1/m Σ[V+(r)-V'+]2 + 1/n Σ[V-(r)-V'-]2 (σ tot)2 - Total variance of the surface electrostatic potential V+(r) positive electrostatic potential in the molecule V'+ average value of the positive electrostatic potential in the molecule V-(r) negative electrostatic potential in the molecule V'- average value of the negative electrostatic potential in the molecule Σ[V+(r)-V'+]2 - this sum is from i=1 till m Σ[V-(r)-V'-]2 - this sum is from i=1 till n Σ[V+(r)-V'+]2 means that Σ[V+(r)-V'+] is in the power of 2 Σ[V-(r)-V'-]2 means that Σ[V-(r)-V'-]2 is in the power of 2 Ontology1271664172453:Toxicophore http://www.drugdesign.com/web/teaching/glossary toxicophore toxicophores A toxicophore is a structural fragment known to be related to some biological toxicity Ontology1271664172453:Translational_enthalpy Translational enthalpy Translational enthalpy of the molecule Ontology1271664172453:Transporter transporter transporters membrane transporter membrane transport protein Membrane-bound protein, which specifically pumps certain compounds across a membrane against a gradient under consumption of energy. Ontology1271664172453:Van_der_Waals_Forces http://www.everyscience.com/Chemistry/Glossary/V.php Van der Waals force Van der Waals forces VDW force VDW forces Van der Waals Forces: Attractive forces that arise between particles as a result of momentary imbalances in the distribution of electrons in the particles. These imbalances produce fluctuating dipoles that can induce similar dipoles in nearby particles, generating a net attractive force. Ontology1271664172453:Van_der_Waals_interaction http://medical-dictionary.thefreedictionary.com/Van+der+Waals+interactions http://polymer.bu.edu/Wasser/robert/work/node8.html http://www.chemguide.co.uk/atoms/bonding/vdw.html van der Waals interaction van der Waals interactions VDW interaction VDW interactions van der Waals dispersion interactions van der Waals dispersion interaction steric interaction steric interactions dispersion interaction dispersion interactions VDW interactions based on interactions between induced dipoles. The potential resulting from these attractive and repulsive interactions is called the Lennard-Jones potential and is described by the following equation: V(r)= A/r6 +B/r12 A - constant B - constant 1/r12 - term describes the short range repulsive potential due to the distortion of the electron clouds at small separations. (r12 means that r is in the power of 12) 1/ r6 - term describes the long--range attractive tail of the potential between two particles. (r6 means r in the power of 6) A weak attractive force between atoms or nonpolar molecules caused by an instantaneous dipole moment of one atom or molecule that induces a similar temporary dipole moment in adjacent atoms or molecules. The origin of van der Waals dispersion forces: temporary fluctuating dipoles. Ontology1271664172453:Vibrational_enthalpy http://www.codessa-pro.com/descriptors/thermodynamic/vem.htm http://www.codessa-pro.com/descriptors/thermodynamic/index.htm Vibrational enthalpy Vibrational enthalpy of the molecule Vibrational enthalpy of the molecule: Hvib=0.5Σhνi + (hνi*exp(-hνi/2KT))/(1-exp(-hνi/2KT)) nj - frequencies of normal vibrations in the molecule h - Planck's constant k - Boltzmann's constant T - absolute temperature (K) Ontology1271664172453:Vibrational_entropy http://www.codessa-pro.com/descriptors/thermodynamic/index.htm http://www.codessa-pro.com/descriptors/thermodynamic/entropy.htm Vibrational entropy Vibrational entropy of the molecule Vibrational entropy of the molecule: Svib= Σ { ((hνj*(exp(-hνj/2KT)))/(KT[1-exp(-hνj/2KT)]) –ln[1-exp(-hνj/2KT)]) } Sum Σ in the formula is from j=1 till α. νj - frequencies of normal vibrations in the molecule h - Planck's constant k - Boltzmann's constant T - absolute temperature (K) Ontology1271664172453:Vibrational_heat_capacity http://www.codessa-pro.com/descriptors/thermodynamic/index.htm http://www.codessa-pro.com/descriptors/thermodynamic/vhcm.htm Vibrational heat capacity Vibrational heat capacity of the molecule Vibrational heat capacity of the molecule: cν=kΣ((hνj/KT)2)*(exp(-hνj/2KT)/(1-exp(-hνj/2KT))) In the formula (Σ) sum is in the power of 2. Sum is from j=1 till α (hνj/KT)2) means that hνj/KT in the power of 2 νj - frequencies of normal vibrations in the molecule h - Planck's constant k - Boltzmann's constant T - absolute temperature (K) Ontology1271664172453:Wiener_index http://www.codessa-pro.com/descriptors/topo/wiener.htm Winer index Winer index W= 0.5ΣDij Σ is over ij till Nsa Nsa- the number of non-hydrogen atom in the molecule Dij - the number of bonds in the shortest path connecting the pair of atoms i amg j. Ontology1271664172453:X-ray protein-protein interaction ontology http://bioportal.bioontology.org/visualize/39508 x-ray x-rays x-ray diffraction X-radiation roentgen ray X-ray image roentgenography roentgenographic RA RADIOGR X-ray scattering Analysis of a diffraction pattern generated by a single crystal. X-rays have a wavelength, typically around 1 Angstrom (the diameter of a hydrogen atom). If a narrow parallel beam of X-rays is directed at a sample of a pure protein, most of the X-rays will pass straight through it. A small fraction, however, will be scattered by the atoms in the sample. If the sample is a well-ordered crystal, the scattered waves will reinforce one another at certain points and will appear as diffraction spots when the X-rays are recorded by a suitable detector. The position and intensity of each spot in the X-ray diffraction pattern contain information about the position and nature of the atoms in the crystal. The three-dimensional structure of a large molecule can be deduced from the electron-density map of its crystal. In recent years X-ray diffraction analysis has become increasingly automated, and now the slowest step is likely to be the production of suitable protein crystals. This requires high concentration of very pure protein and empirical searching for the proper crystallisation conditions. Ontology1271664172453:X-ray_fiber_diffraction Protein-protein Interaction ontology. http://bioportal.bioontology.org/visualize/39508 X-ray fiber diffraction X-ray x-ray fiber diffrac Analysis of diffraction pattern of a partially ordered sample composed of fibers oriented parallel to each other using Xray. Ontology1271664172453:X-ray_powder_diffraction Protein-protein interaction http://bioportal.bioontology.org/visualize/39508 X-ray powder diffraction X-ray x-ray powder diffrac Analysis of a diffraction pattern generated by an isotropic sample composed of many randomly oriented crystals. Ontology1271664172453:absolute_and_relative_numbers_of_certain_chemical_groups_and_functionalities http://www.codessa-pro.com/descriptors/const.htm absolute and relative numbers of certain chemical groups and functionalities absolute and relative numbers of certain chemical groups and functionalities in the molecule Ontology1271664172453:activation_energy http://www.shodor.org/chemviz/glossary.html http://www.science.uwaterloo.ca/~cchieh/cact/c123/eactivat.html http://www.cartage.org.lb/en/themes/Sciences/Chemistry/Organicchemistry/Common/Common.htm activation energy Energy of activation Arrhenius activation energy activation barrier activation barriers E(a) k=Aexp(-Ea/RT) Ea - activation energy (Arrhenius activation energy) k - rate constant A - the pre-exponential factor or simply the prefactor R - the gas constant T - tempreture where the pre-exponential factor A is assumed to be independent of temperature , R is the gas constant, and T the temperature in K. Taking the natural logarithm of this equation gives: ln k = ln A - Ea/(RT) or ln k = -Ea/(RT) + constant or ln k = -(Ea/R)(1/T) + constant These equations indicate that the plot of ln k vs. 1/T is a straight line, with a slope of -Ea/R. These equations provide the basis for the experimental determination of Ea. 1) Activation energy Arrhenius calculation from two temperatures. http://www.calctool.org/CALC/chem/kinetics/act_en 2) http://www.shodor.org/UNChem/advanced/kin/arrhenius.html 3) http://home.fuse.net/clymer/arr/ The miminmum energy which reacting species must possess in order to be able to form an 'activated complex', or 'transition state', before proceeding to the products. The activation energy (Ea) may be derived from the temperature dependence of the reaction rate using the Arrhenius equation. Activation energy can be thought of as the height of the potential barrier separating two minima of potential energy (of the reactants and products of a reaction). For a chemical reaction to proceed at a reasonable rate, there should exist an appreciable number of molecules with energy equal to or greater than the activation energy. Ontology1271664172453:activator http://www.peakagents.ca/glossary/a2.htm activator activators Substance that acts as a catalyst, speeding up a chemical reaction without being affected by the reaction. Ontology1271664172453:active_site http://www.encyclopedia.com/doc/1O6-activesite.html active site active sites active centre active center reactive site reactive sites catalytic site catalytic sites active-sites active-site The site on the surface of an enzyme molecule that binds and acts on the substrate molecule. The properties of an active site are determined by the three-dimensional arrangement of the polypeptide chains of the enzyme and their constituent amino acids. These govern the nature of the interaction that takes place and hence the degree of substrate specificity and susceptibility to inhibition. Ontology1271664172453:activity NCI/PT UMLS activity activities Calculation of molecular properties and bioactivity prediction: link: http://www.molinspiration.com/cgi-bin/properties An action taken in pursuit of an object; the state of being active. Ontology1271664172453:activity_cliffs Peltason, L., et al., Exploration of structure-activity relationship determinants in analogue series. J Med Chem, 2009. 52(10): p. 3212-24 activity cliff activity cliffs Small changes in molecular structure lead to dramatic (positive or negative) biological effects Ontology1271664172453:activity_landscape Maggiora, G.M., On outliers and activity cliffs--why QSAR often disappoints. J Chem Inf Model, 2006. 46(4): p. 1535. activity landscape activity landscapes structure-activity landscape SAR discontinuity scoring Activity landscape associated with a given assay, which is related to the chemical-space representation used to characterize the set of compounds assayed. Activity landscapes are generally of high dimension (>3) and depend on the nature of the assay (e.g., enzyme-based, cell-based, etc.), on the region(s) of chemical space from which the compounds are drawn, on the density distribution of the compounds in these regions, and, most importantly, on the nature of the molecular representation used. A typical N-dimensional activity landscape is composed of an (N-1)-dimensional chemical space; each dimension is described by a coordinate, which is generally defined by a single molecular descriptor or combination of descriptors. The Nth dimension is defined by the activity space that is derived from the measured activity of each of the assayed compounds. In three dimensions activity landscapes are closely akin to Nature’s landscapes. Ontology1271664172453:allosteric_antagonist Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. allosteric antagonist allosteric antagonists allotopic antagonists Allosteric (allotopic) antagonists are modulators that reduce orthosteric ligand affinity and/or agonist efficacy. Ontology1271664172453:allosteric_inhibitor http://www.biology-online.org/dictionary/Allosteric_Inhibitors allosteric inhibitor allosteric inhibitors Inhibitors act as 'modulators' in enzyme execution as they can attach themselves to a molecule that will alter the binding Site for the enzyme, rendering it unusable and therefore rendering the enzyme inactive. Change the conformation of enzyme to avoid access for the substrate. Ontology1271664172453:allosteric_modulator Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. allotopic modulator allotopic modulators allosteric modelator allosteric modelators allosteric modulation A ligand that increases or decreases the action of an (primary or orthosteric) agonist or antagonist by combining with a distinct (allosteric or allotopic) site on the receptor macromolecule. Ontology1271664172453:allosteric_site C.G Wermuth, et al., Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998). Pure Appl. Chem., 1998. 70(5): p. 1129-1143. http://www.reportbuyer.com/samples/c37bead2a8f831492fcaa97028cb9b76.pdf allosteric site allosteric sites allosteric regulatory site regulatory sites allosteric binding site allosteric binding sites allosteric binding pocket allosteric binding pockets Allosteric binding sites are contained in many enzymes and receptors. As a consequence of the binding to allosteric binding sites, the interaction with the normal ligand may be either enhanced or reduced. A binding site on the receptor that is topographically distinct from (does not overlap with) the orthosteric site. Ontology1271664172453:amphiphilicity http://www.drugdesign.com/web/teaching/glossary amphiphilicity amphiphilicity index amphipathic amphiphil With both hydrophilic and hydrophobic properties. Ontology1271664172453:apolar_surface_area apolar surface area apolar surface areas Ontology1271664172453:atropisomer http://goldbook.iupac.org/A00511.html atropisomer atropisomers atropisomeric A subclass of conformers which can be isolated as separate chemical species and which arise from restricted rotation about a single bond, e.g. ortho-substituted biphenyl, 1,1,2,2-tetra-tert-butylethane. Ontology1271664172453:bending_energy Kholodovych, V., Molecular Mechanics, University of Medicine&Dentistry of New Jersey (UMDN J). bending energy bending energies BE energy of bending bending Hooke's law: E=Σk(Θ-Θo)2 ( (Θ-Θo)2 means r in the power of two) Σ-sum over the Θ F- force k- controls the stiffness of the angle spring Θ- angle position after bending Θo - equilibrium angle E- estimates energy associated with vibration about equilibrium bond angle. Energy of bending bond angles from their natural values. Ontology1271664172453:binding_Gibbs_free_energy http://en.wikibooks.org/wiki/Structural_Biochemistry/Molecular_Moldeling/Molecular_Docking Holdgate, G.A. and W.H. Ward, Measurements of binding thermodynamics in drug discovery. Drug Discov Today, 2005. 10(22): p. 1543-50. binding Gibbs free energy free energy of protein-ligand binding free energy of binding Gibbs free energy of binding binding free energy binding free energies [NL] protein-ligand complex The change in Gibbs free energy (ΔG) under arbitrary conditions, for the formation of NL is related to standard Gibbs free energy change (ΔGo), under defined conditions (e.g M N and 1 M L at pH 7 and T=25 C) ΔG=ΔGo+R*T*ln( [NL] / ([N][L]) ) ΔGo=-R*T*ln( [NL] / ([N][L]) ) = -RT lnKb = RT lnKd - at equilibrium under standart conditions, where ΔG=0 Kb - binding constant (equilibrium association constant) Kd - dissociating constant (equilibrium dissociation constant). It depends upon the free energy of binding ΔGo R - gas constant T -absolute tempreture Ontology1271664172453:binding_activity binding activity binding activities ligand binding activity receptor binding activity Ontology1271664172453:binding_model binding model binding models Ontology1271664172453:binding_site_properties binding site property binding site properties properties of binding site Ontology1271664172453:binding_site_volume binding site volume cavity volume active site volume Volume which is occupied by the binding site. Ontology1271664172453:bioactive_comformation http://www.drugdesign.com/web/teaching/glossary bioactive conformation bioactive conformations "bioactive" conformation "bioactive" conformations biolologically active conformation biolologically active conformations active conformation active conformations bound conformation bound conformations The geometry adopted by a ligand when it binds to its biological target. Ontology1271664172453:biological_activity http://www.springerlink.com/content/fn26h244j41v84w2/ biological activity biological activities bioactive bioactivity A definition of biological activity is proposed that is superficially analogous to the equation relating the thermodynamic activity of a solute to its concentration via an activity coefficient. The biological activity of a molecular entity is defined as A=cf, where A is the activity, c the amount-of-substance concentration, and f is a parameter designated as “inherent activity.” Ontology1271664172453:biotransformation_ability http://www.chem.qmul.ac.uk/iupac/medchem/ah.html#b4 biotransformation ability biotransformation abilities Ability to participate in the biotransformation. Biotransformation is the chemical conversion of substances by living organisms or enzyme preparations. Ontology1271664172453:bound_ligand_volume bound ligand volume volume of bound ligand bound volume bound volumes ligand volume Volume which is occupied by the bound ligand in the binding site. Ontology1271664172453:buriness buriness bury buried Ontology1271664172453:charge_distribution http://www.ac.wwu.edu/~vawter/PhysicsNet/Topics/Gauss/SpacialCharge.html charge distribution charge distributions surface charge distribution surface charge distributions electrostatic charge distribution electrostatic charge distributions spatial charge distribution spatial charge distributions molecular electrostatic charge distributions molecular electrostatic charge distribution ligand-charge distribution radially isotropic charge distribution Destribition of electric charge (positive, negative charges) on a line or surface or volume. Ontology1271664172453:chemical_antagonism http://science.jrank.org/pages/24802/antagonist.html chemical antagonism biochemical antagonism biochemical antagonist biochemical antagonists chemical antagonist chemical antagonists Antagonism may also result from combination with the substance being antagonized (chemical antagonism). Ontology1271664172453:cis-trans_isomers http://goldbook.iupac.org/C01093.html cis and trans isomers Cis-trans isomers: Stereoisomeric olefins or cycloalkanes (or hetero-analogues) which differ in the positions of atoms (or groups) relative to a reference plane: in the cis-isomer the atoms are on the same side, in the trans-isomer they are on opposite sides. Ontology1271664172453:co-agonist http://en.wikipedia.org/wiki/Agonist coagonist coagonists co-agonist co-agonists A co-agonist works with other co-agonists to produce the desired effect together. NMDA receptor activation requires the binding of both of its glutamate and glycine co-agonists. An antagonist blocks a receptor from activation by agonists. Ontology1271664172453:coactivator http://en.wikipedia.org/wiki/Coactivator_(genetics) A coactivator is a protein that increases gene expression by binding to an activator (or transcription factor) which contains a DNA binding domain. coactivator coactivators co-activator co-activators Ontology1271664172453:combining_site http://www.nlm.nih.gov/mesh/ combining site combining sites reactive site reactive sites The reactive parts of macromolecule that directly participate in its specific combination with another molecule. Ontology1271664172453:competitive_inhibitor competitive inhibitor competitive inhibitors Competes with substrate for enzyme binding. Ontology1271664172453:competitive_interaction http://www.nlm.nih.gov/mesh/ competitive interactions competitive interaction The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Ontology1271664172453:concavity http://www.thefreedictionary.com/concavity concavity concavities concave The state of being curved like the inner surface of a sphere. Ontology1271664172453:configurational_entropy http://www.pnas.org/content/104/5/1534.full http://en.wikipedia.org/wiki/Configuration_entropy Gilson, M.K. and H.X. Zhou, Calculation of protein-ligand binding affinities. Annu Rev Biophys Biomol Struct, 2007. 36: p. 21-42. configurational entropy configurational entropies S(configuration) = S(vibration)+S(conformational) S(configuration) - configuration entropy S(vibration) - vibration entropy S(conformational)- conformation entropy S(conformational) = -RΣPjLn(Pj) M - number of energy wells Pj is the probability of occupying energy well j. S(vibration) = -Rln( (< E >j - μj) / T) < E >j - is the average energy of well j μj - is its standard chemical potential Σ is from j to M configuration entropy is the portion of a system's entropy that is related to the position of its constituent particles rather than to their velocity or momentum. It is physically related to the number of ways of arranging all the particles of the system while maintaining some overall set of specified system properties, such as energy. Configuration entropy: the entropy associated with motions of the ligand and/or protein. Ontology1271664172453:conformation http://goldbook.iupac.org/C01258.html conformation conformations The spatial arrangement of the atoms affording distinction between stereoisomers which can be interconverted by rotations about formally single bonds. Some authorities extend the term to include inversion at trigonal pyramidal centres and other polytopal rearrangements. Ontology1271664172453:conformational_entropy http://www.pnas.org/content/104/5/1534.full http://www.thefreedictionary.com/conformational+entropy conformational entropy S(conformational)- conformation entropy S(conformational) = -RΣPjLn(Pj) M - number of energy wells Pj is the probability of occupying energy well j. Σ is from j to M conformational entropy - entropy calculated from the probability that a state could be reached by chance alone. Ontology1271664172453:conformational_sampling_method Conformational sampling method Conformational sampling methods conformational search method conformational search conformational sampling techniques conformational sampling technique Conformational sampling The method which allows to generate different ligand conformations in a ligand binding site. Ontology1271664172453:conformer http://goldbook.iupac.org/C01262.html conformer conformers multiconformer multi-conformer ligand conformer One of a set of stereoisomers, each of which is characterized by a conformation corresponding to a distinct potential energy minimum. Ontology1271664172453:contact_surface http://www.netsci.org/Science/Compchem/feature14e.html contact surface contact surfaces The contact surface is the part of the van der Waals surface that can be touched by a water-sized probe sphere. Ontology1271664172453:cooperative_binding http://en.wikipedia.org/wiki/Cooperative_binding http://academic.brooklyn.cuny.edu/biology/bio4fv/page/coopera.htm cooperative binding The term cooperative binding derives from the property that the binding of one molecule of substrate makes it easier for the second molecule of substrate to bind.A macromolecule exhibits cooperative binding if its affinity for its ligand changes with the amount of ligand already bound. Ontology1271664172453:cooperativity Wermuth, C.G., et al., Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998). Pure Appl. Chem., 1998. 70(5): p. 1129-1143. http://goldbook.iupac.org/C01325.html cooperativity cooperativities co-operativity co-operativities Cooperativity is the interaction process by which binding of a ligand to one site on a macromolecule (enzyme, receptor, etc.) influences binding at a second site, e.g. between the substrate binding sites of an allosteric enzyme. Binding of a substrate molecule to one binding site changes the affinity of the binding sites on the other subunits to the substrate by induction of a conformation change at the other binding sites. Cooperative enzymes typically display a sigmoid (S-shaped) plot of the reaction rate against substrate concentration. Ontology1271664172453:cross_docking http://autodock.scripps.edu/faqs-help/glossary/cross-docking cross docking cross dockings The process of taking a series of complexes of ligand-receptor pairs, and docking every ligand to every receptor. This can be interesting to study the specificity of the receptors and ligands, and when the receptors are all the same protein but in different conformations, this can yield valuable information about the effects of induced fit upon binding. Ontology1271664172453:desolvation_energy Enzyme Functionality: Design: Engineering, and Screening, ed. A. Svendsen. 2003: CRC Pres Moman, E., Introduction to Molecular Docking, Pharmaceutical and Medicinal Chemistry, Saarland University. desolvation energy desolvation energies energy of desolvation desolvation ΔGdesolv = Wdesolv Σi (C), j (Si * Vj * exp ( -rij2 / (2 * σ2) ) rij2 means rij in the power of 2 σ2 means σ in the power of 2 Desolvation energy, this is the energy of transfer of titratable or pH-sensitive site from standart condition (model compound in solution) to its place in the protein molecule. As far as only electrostatic interactions are considered, desolvation energy is then the difference between self energies when the titratable or pH-sensitive site is considered as a model compound in solution (S) and when it is at its location in protein molecule (P). Ontology1271664172453:diastereoisomer http://goldbook.iupac.org/D01679.html diastereomer diastereomers diastereomeric diastereoisomerism Diastereoisomers (or diastereomers) are stereoisomers not related as mirror images. Diastereoisomers are characterized by differences in physical properties, and by some differences in chemical behaviour towards achiral as well as chiral reagents. Ontology1271664172453:dipole-induced_dipole_force http://www.chem.unsw.edu.au/coursenotes/CHEM1/nonunipass/HainesIMF/dipoleinddipole dipole-induced dipole force dipole-induced dipole forces A polar molecule produces an electric field which can distort the electron cloud of a nearby molecule. If a non-polar molecule is brought near a polar molecule the field from the polar molecule can induce a dipole moment in a nearby non-polar molecule . This will cause the an attraction between the molecules. The size of the induced dipole depends on the ease with which the electron distribution in the non-polar molecule can be distorted by the electric field of the polar molecule. This is a property of any molecule called its polarizability. In general molecular polarisability is larger for molecules with a larger volume (for example, molecules containing atoms with large atomic number). Ontology1271664172453:dipole_dipole_interaction http://goldbook.iupac.org/D01758.html http://www.britannica.com/EBchecked/topic/684121/chemical-bonding/43433/Dispersion-interaction dipole-dipole interaction dipole-dipole interactions dipole dipole interaction dipole dipole interactions dipole interaction dipole interactions dispersion interaction dispersion interactions induced-dipole–induced-dipole interaction induced-dipole–induced-dipole interactions Intermolecular or intramolecular interaction between molecules or groups having a permanent electric dipole moment. The strength of the interaction depends on the distance and relative orientation of the dipoles. The term applies also to intramolecular interactions between bonds having permanent dipole moments. Ontology1271664172453:dissociation_constant http://chemistry-dictionary.com/definition/dissociation.html http://www.dissociationconstant.com/ dissociation constant dissociation constants equilibrium dissociation constant system's dissociation constant kinetic equilibrium dissociation constant secondary dissociation constant first dissociation constant primary dissociation constant enzyme-ligand dissociation constant A general example is the dissociation of the compound AB into A+B which can be written as         AB ⇔ A + B It can be calculated from the dissociation how much in the solution is on the form AB, A and B constant. However, before the calculation it is important to stress that the dissociation of AB into A and B is a reversible process. A and B can assemble back into AB. In this very simple example, the dissociation constant can be written as Kd = ([A] . [B]) / [AB] More complicated cases are calculated using the same method and in most cases the problem is more complicated. The general equation is written as        AxBy ⇔ xA + yB In this case the dissociation constant is written as: Kd = ([A]x . [B]y) / [AxBy] Equilibrium constant that applies to the dissociation of a comples ion into a simple ion and coordinating species (ligands). Equilibrium dissociation constant for ligandreceptor interactions is- K. Ontology1271664172453:docking Protein-protein interaction http://bioportal.bioontology.org/visualize/39508 Lesk, V., Modeling Protein Complexes. 2006. http://en.wikibooks.org/wiki/Structural_Biochemistry/Molecular_Moldeling/Molecular_Docking docking dockings molecular docking simulated docking docking simulation docking simulations docking approach docking study docking studies ligand docking protein-ligand docking molecular docking procedure docking procedure In the field of molecular modeling, docking is a method which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using for example scoring functions. Docking is frequently used to predict the binding orientation of small molecule drug candidates to their protein targets in order to in turn predict the affinity and activity of the small molecule. Hence docking plays an important role in the rational design of drugs. Given the biological and pharmaceutical significance of molecular docking, considerable efforts have been directed towards improving the methods used to predict docking. Predicts the structure of a protein-protein complex from the unbound structures of its components. The initial approach in the majority of docking procedures is based largely on the 'rigid-body' assumption, whereby the proteins are treated as solid objects. Initial scoring of a complex is based on geometric fit or surface complementarity. This generally requires some knowledge of the binding site to limit the number of solutions. Exploration of the space of possible protein-ligand geometries. Given: receptor binding pocket and ligand. Task: find correct binding pose. Docking two molecules means constructing the coordinates of the bound state.Bound state is called the complexDocking two molecules means constructing the coordinates of the bound state. Bound state is called the complex. Ontology1271664172453:docking_output docking output docking outputs output of docking The output of a programm which performs protein-ligand docking. Ontology1271664172453:docking_site docking site docking sites The protein site to which the ligands were docked. Ontology1271664172453:docking_type docking type docking types type of docking Ontology1271664172453:efficacy http://www.chem.qmul.ac.uk/iupac/medchem/ah.html#e1 efficacy efficacies Efficacy is the property that enables drugs to produce responses. It is convenient to differentiate the properties of drugs into two groups, those which cause them to associate with the receptors (affinity) and those that produce stimulus (Efficacy). This term is often used to characterize the level of maximal responses induced by agonists. In fact, not all agonists of a receptor are capable of inducing identical levels of maximal responses. Maximal response depends on the efficiency of receptor coupling, i.e., from the cascade of events, which, from the binding of the drug to the receptor, leads to the observed biological effect. Ontology1271664172453:electric_dipole_moment http://chemistry.umeche.maine.edu/CHY251/Terms1.html dipole moment electric dipole moment electric dipole moments dipole moment molecular dipole p=Q*d p - dipole molent Q - electric charge d -is the displacement vector pointing from the negative charge to the positive charge A quantitative measure of the asymmetry of electron distribution in a molecule; = the distance of separation of charge times the magnitude of the charge. Ontology1271664172453:empirical_approach MOE:http://www.chemcomp.com/software.htm empirical approach empirical approaches empirical scoring function empirical scoring functions empirical scoring empirical potential Empirical scoring functions are force fields calibrated to a particular training set of complexes with known 3D structures (X-ray data) and experimental biological activities. Each type of force field contribution is multiplied by a weighting coefficient (determibed empirically by the parameterization study). In order to be computationally efficient some methods use a restricted number of force-field terms, for example "Ligscore" uses only three terms: Van der Waals, polarity and desolvation. Ontology1271664172453:enantiomer http://goldbook.iupac.org/E02069.html Enantiomer Enantiomers One of a pair of molecular entities which are mirror images of each other and non-superposable. Ontology1271664172453:endogenous_agonist en.wikipedia.org/wiki/Endogenous_agonist endogenous agonist endogenous agonists In pharmacology, an endogenous agonist for a particular receptor is a compound naturally produced by the body which binds to and activates that receptor. For example, the endogenous agonist for serotonin receptors is serotonin, and the endogenous agonist for dopamine receptors is dopamine Ontology1271664172453:energy_minimization http://cmm.cit.nih.gov/intro_simulation/node22.html Funkhouser, T., Protein-Ligand docking, Princeton University. energy minimization energy-minimization energy optimization geometry optimization minimization procedure minimization procedures In the context of macromolecules, the function to be optimized (minimized) is an energy. The energy landscape of a biomolecule possesses an enormous number of minima, or conformational substates. Nonetheless, the goal of energy minimization is simply to find the local energy minimum, i.e., the bottom of the energy well occupied by the initial conformation. The energy at this local minimum may be much higher than the energy of the global minimum. - Start from a random or specific state (position, orientation, conformation) - Move in direction indicated by derivatives of energy function - Stop when reach local minimum Ontology1271664172453:entropic_effect entropic effect entropic effects Ontology1271664172453:equilibrium_constant http://www.cartage.org.lb/en/themes/Sciences/Chemistry/Organicchemistry/Common/Common.htm equlibrium constant According to the law of mass action, for any reversible chemical reaction: aA + bB = cC + dD, the equilibrium constant (K)is defined as: K = ([C]c[D]d)/([A]a[B]b) [C]c means C is in the power of c [D]d means D is in the power of d [A]a means A is in the power of a [B]b means B is in the power of b Chemical Equilibrium Calculator link: http://www.changbioscience.com/biochem/keq.html Ontology1271664172453:experiment http://www.thefreedictionary.com/experiment experiment experiments experimental research experimental study A test under controlled conditions that is made to demonstrate a known truth, examine the validity of a hypothesis, or determine the efficacy of something previously untried. Ontology1271664172453:experimental_knowledge_based Protein-protein interaction ontology http://bioportal.bioontology.org/visualize/39508 experimental knowledge based experimental info Predictive algorithms that rely on the information obtained by experimental results. Ontology1271664172453:flexible_combining_site Zimmermann, J., et al., Molecular description of flexibility in an antibody combining site. J Phys Chem B, 2010. 114(21): p. 7359-70 Flexible combining site flexible combining sites Flexible combining site is a combining site which is able to adopt different conformations that recognize different foreign molecules (or antigens). Ontology1271664172453:four_point_pharmacophore_fingerprint Taboureau, O., 3D descriptors and fingerprints, Chemoinformatics, CBS-BioCentrum. four point pharmacophore fingerprint four point pharmacophore fingerprints four-point pharmacophore fingerprint four-point pharmacophore fingerprints Each fragment consists of 4 pharmacophoric points. – the distances between each pair of these points are binned and used to set fingerprint bits. Main advantage is that it takes account the conformational flexibility and chirality which can be also is main weakness. Ontology1271664172453:fragmentation_method MOE:http://www.chemcomp.com/software.htm fragmentation method fragmentation methods fragmentation approach fragment-based ligand docking technique Method break down the molecule into small rigid fragments. The fragments are then reassembled in the binding pocket. Two different approaches are used for reassembling the disconnected moieties: the place-and-join and incremental aproach. One of the advantages of fragmentation methods is that they enable efficient pruning of the search tree and early elimination of solutions that are not worth assessment. Ontology1271664172453:full_agonist http://pharmrev.aspetjournals.org/content/55/4/597/T6.expansion full agonist full agonists When the receptor stimulus induced by an agonist reaches the maximal response capability of the system (tissue), then it will produce the system maximal response and be a full agonist in that system. If the maximum tissue response is reached at less than full receptor occupancy it results in a so-called a spare receptor situation. Several agonists may thus elicit the same maximal response, albeit at different receptor occupancies. They are all full agonists in that experimental system but have different efficacies. This designation of full vs. partial agonist is systemdependent, and a full agonist for one tissue or measurement may be a partial agonist in another. Ontology1271664172453:functional_antagonism http://medical-dictionary.thefreedictionary.com/functional+antagonism functional antagonism (in pharmacology) a situation in which two agonists interact with different receptors and produce opposing effects Ontology1271664172453:functional_antagonist functional antagonist functional antagonists The compound which reduces the receptor activity via alternative routes, not by direct competition with agonists. Ontology1271664172453:geometrical_properties geometrical property geometrical properties Geometrical properties are the properties concerned with shape, volume, size, space. Ontology1271664172453:heterotropic_effect http://science.jrank.org/pages/32507/heterotropic.html heterotropic heterotropic effect heterotropic effects heterotropic cooperative binding Describing an allosteric effect in which interaction occurs between nonidentical ligands; the effect may be either cooperative or antagonistic. The term is applied also to such an interaction, to an allosteric enzyme for which different substances act as the substrate and the effector, to the regulation of such an allosteric system, etc. Ontology1271664172453:homotropic_effect http://science.jrank.org/pages/32795/homotropic.html homotropic homotropic effect homotropic effects Describing an allosteric effect in which interaction occurs between identical ligands; the effect appears to be always cooperative. The term is applied also to such an interaction in the case of an allosteric enzyme for which the same substance acts as both the substrate and the allosteric effector, etc. Ontology1271664172453:hydropathy http://www.nature.com/nrd/journal/v1/n9/glossary/nrd893_glossary.html hydropathy hydropathic The analysis of the hydrophobic and hydrophilic characteristics of molecules Ontology1271664172453:hydrophilicity http://antoine.frostburg.edu/chem/senese/101/solutions/glossary.shtml hydrophilicity hydrophilic A polar molecule or group that can form strong hydrogen bonds with water. "water loving" Ontology1271664172453:hydrophobic_contact_surface hydrophobic contact surface hydrophobic contact surfaces Ontology1271664172453:hydrophobic_surface_area hydrophobic surface area hydrophobic surface areas Ontology1271664172453:indirect_antagonism http://pharmrev.aspetjournals.org/content/55/4/597/T1.expansion indirect antagonism indirect antagonist indirect antagonists Competition by the inhibitor for the binding site of an intermediate macromolecule that links the binding of the administered agonist to the effect observed. Ontology1271664172453:induced_fit_model http://cnx.org/content/m11456/latest/ induced-fit model induced-fit models IF induced-fit induced-fit mechanism induced fit mechanism induced-fit binding induced-fit process induced-fit A more accurate view of this process was first presented by Koshland in the induced fit model. In this model the three dimensional structure of the ligand and the receptor adapt to each other during the binding process. It is important to note that not only the structure of the ligand but also the structure of the receptor changes during the binding process. This occurs because the introduction of a ligand modifies the chemical and structural environment of the receptor. As a result, the unbound protein conformational substates, corresponding to the low energy regions of the protein energy landscape are likely to change. The induced-fit mechanism corresponds to ligand binding in the unbound ground state. Ontology1271664172453:interaction_detection interaction detection detection of interaction Ontology1271664172453:interaction_prediction Protein-protein interaction ontology. http://bioportal.bioontology.org/visualize/39508 interaction prediction interaction predictions in silico methods predicted interac prediction of interaction prediction of interactions Computational methods to predict an interaction. Ontology1271664172453:interaction_simulation interaction simulation interaction simulations simulation of interaction Ontology1271664172453:interaction_site http://www.nature.com/nrd/journal/v4/n8/glossary/nrd1799_glossary.html Protein-Ligand Interactions: From Molecular Recognition to Drug Design (Methods and Principles in Medicinal Chemistry), ed. H.-J. Boehm and G. Schneider. Vol. 19. 2003: WIley-VCH interaction site interaction sites ligand interaction site protein interaction site A position in space that is not occupied by the receptor and in which a ligand atom favourably interacts with the receptor. Ontology1271664172453:intercalator http://www.cancer.gov/dictionary/?CdrID=318816 intercalator intercalators intercalating agents intercalating agent agents, intercalating iIntercalative Compounds compounds, Intercalative intercalating Ligand ligands, intercalating intercalators intercalator DNA Intercalating Agent INTERCALATIVE CPDS In biochemistry, a type of molecule that binds to DNA and inserts itself into the DNA structure. Some intercalators are used as treatments for cancer. Ontology1271664172453:intermolecular_interaction http://en.wikipedia.org/wiki/Intermolecular_force Intermolecular interaction Intermolecular interactions Intermolecular forces Intermolecular force intermolecular interactions Interaction between separate molecules. Intermolecular forces are forces that act between stable molecules or between functional groups of macromolecules. Ontology1271664172453:intramolecular_interaction http://academic.pgcc.edu/~ssinex/DII_103/intramol.htm intramolecular interaction intramolecular interactions intramolecular forces intramolecular force It is an interactions within the molecule. Ontology1271664172453:inverse_agonist http://pharmrev.aspetjournals.org/content/55/4/597/T6.expansion inverse agonist inverse agonists inverse agonism negative antagonists negative antagonist A ligand that by binding to receptors reduces the fraction of them in an active conformation An inverse agonist may combine either with the same site as a conventional agonist, or with a different site on the receptor macromolecule Ontology1271664172453:irreversible_antagonist Goodman and Gilman's Manual of Pharmacology and Therapeutics. (11th edition, 2008). p25. ISBN 0071443436 irreversible antagonist irreversible antagonists An irreversible antagonist is a type of antagonist that binds permanently to a receptor, either by forming a covalent bond to the active site, or alternatively just by binding so tightly that the rate of dissociation is effectively zero at relevant time scales Ontology1271664172453:irreversible_competitive_antagonism http://www.chemie.de/lexikon/e/Receptor_antagonist/ irreversible competitive antagonism some antagonists, when in close enough proximity to their binding site, may form a stable covalent bond with receptor (irreversible competitive antagonism), and the antagonism becomes insurmountable when no spare receptors remain. Competitive irreversible antagonists like competitive antagonists also involves competition between agonist and antagonists of the receptor but stronger binding forces, usually involving covalent binding of the antagonist to the agonist binding site on the receptor, in which case there is a period before the covalent bond forms determined by receptor-ligand kinetics during which competing ligands can prevent the inhibition. Once binding of the antagonist occurs however even at high agonist concentrations the effect of the antagonist cannot be fully reversed. Ontology1271664172453:irreversible_inhibitor Motulsky, H. and A. Christopoulos, Fitting Models to Biological Data Using Linear and Nonlinear Regression. 2003, Oxford, UK: Oxford Press. irreversible inhibitor irreversible inhibitors inactivator forms a stable chemical linkage to the enzyme Ontology1271664172453:irreversible_noncompetitive_antagonism Noncompetitive antagonism which is irreversible. Ontology1271664172453:isotopomer http://goldbook.iupac.org/I03352.html Isotopomer Isotopomers Isomers having the same number of each isotopic atom but differing in their positions. The term is a contraction of 'isotopic isomer'. Isotopomers can be either constitutional isomers (e.g. CH2DCH=O and CH3CD=O) or isotopic stereoisomers [e.g. (R)- and (S)-CH3CHDOH or (Z)- and (E)-CH3CH=CHD]. Ontology1271664172453:knowledge-based_approach MOE:http://www.chemcomp.com/software.htm knowledge-based approach knowledge-based approaches knowledge-based scoring knowledge-based energy function knowledge-based scoring function knowledge-based potential scoring function knowledge-based pair-potentials knowledge-based pair-potential knowledge-based potential knowledge-based potentials The knowledge-based approach is based on statistical analyses of X-ray (PDB) complexes; its aims at deriving elementary energy contributions for each type of non-bonded atom pair interaction between a protein and a ligand. Statistical analyses calculate the distribution of occurrence frequencies in the distances for each type of pair of interactions (the more often an interatomic distance occurs, the more favorable it is). Distribution of occurrence frequencies can be translated into free energy scores for a given pair of atoms at a given distance using Bolzmann distribution. The interaction potential generated is usually called "potential of mean force" (PMF) and is constructed for each type of interaction. Ontology1271664172453:knowledge-guided_scoring Cheng, T., Z. Liu, and R. Wang, A knowledge-guided strategy for improving the accuracy of scoring functions in binding affinity prediction. BMC Bioinformatics, 2010. 11: p. 193. knowledge-guided scoring KGS The key idea is that the unknown binding affinity of a given protein-ligand complex can be estimated more reliably based on the known binding affinity of an appropriate reference complex. The reference complex is required to share a similar pattern of key protein-ligand interactions with the given protein-ligand complex. For this purpose, our KGS strategy utilizes a sufficient number of relevant protein-ligand complexes with known structures and binding affinities as a knowledge set. The key protein-ligand interactions in each complex are summarized as a pharmacophore model, which can be elucidated by an automatic algorithm. The knowledge set is then searched through for the appropriate reference complex for any given protein-ligand complex. Ontology1271664172453:ligand_binding_site http://www.nlm.nih.gov/research/umls/ http://www.techfak.uni-bielefeld.de/bcd/ForAll/Introd/drugdesign.html http://dictionary.sensagent.com/binding+site/en-en/ Xie, L., et al., Knowledge Discovery of Protein-Ligand Interaction Network, in Conference on Semantics in Healthcare and Life Sciences (CSHALS). 2010: Cambridge/Boston, MA. ligand binding site ligand binding sites active site binding cavity binding cavities binding envelope binding pocket binding pockets binding site binding sites receptor binding site receptor binding sites ligand binding cavities ligand binding cavity ligand-binding pocket ligand-binding pockets Ligand binding site is a region of protein that physically interacts stereospecifically, and usually at high affinity, with a specific ligand, substrate, or specific domain of some complex target biomolecule, such as protein, lipid, carbohydrate, or nucleic acid. Tipically, but not nessesarily, the interaction results in protein conformational alteration and functional modification. Ontology1271664172453:lipophobicity http://www.webster-dictionary.net/definition/lipophobic lipophobicity lipophobic Not soluble in lipids, or in non-polar solvents; - of chemical substances or parts of molecules; as, the lipophobic end of a detergent is solvated in water. Contrasted to lipophilic or nonpolar. "lipid hating" Ontology1271664172453:lock-and-key_model http://cnx.org/content/m11456/latest/ lock-and-key lock and key lock-and-key model lock-and-key models 'lock-and-key' model lock-and-key mechanism lock-and-key principle lock-and-key concept In this model the three dimensional structure of the ligand and the receptor complement each other in the same way that a lock complements a key. However, further work confirmed that the lock-and-key model is not the most correct description for ligand binding. Ontology1271664172453:mQSAR mQSAR multi-dimensional quantitative structure-activity relationships multi-dimensional quantitative structure-activity relationship It is n-dimensional (multi-dimensional) quantitative structure-activity relationship. Ontology1271664172453:mechanism_of_action http://www.webmd.com/treating-her2-breast-cancer/breast-cancer-glossary-3 http://www.ce-studios.com/obagi/glossary.html mechanism of action The method by which a drug or therapy affects the body in order to produce a specific result. The way by which a procedure or product works to produce an intended effect. Ontology1271664172453:mode_of_action http://www.nature.com/nrg/journal/v5/n12/glossary/nrg1493_glossary.html http://www.anticancer.de/en/glossary.html mode of action MOA The sequence of events from the absorption of a compound into an organism to a toxic outcome or death. The individual steps and processes by which a drug works. Ontology1271664172453:mode_of_binding http://www.drugdesign.com/web/teaching/glossary mode of binding modes of binding binding mode binding modes ligand binding mode ligand binding modes receptor binding mode receptor binding modes binding geometry binding geometries Orientation and geometry adopted by a chemical substance when it is bound to its receptor. Ontology1271664172453:mode_of_interaction mode of interaction modes of interaction interaction mode interaction modes Ontology1271664172453:modulator Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. modulator modulators A ligand that increases or descreases the action of an agonists by combining with a distinct (allosteric) site on the receptor macromolecule. Ontology1271664172453:molecular_surface http://www.netsci.org/Science/Compchem/feature14e.html molecular surface molecular surfaces molecular surface area molecular surface areas The molecular surface is the surface traced by the inward-facing surface of the probe sphere. Ontology1271664172453:molecular_weight http://chemistry.about.com/od/dictionariesglossaries/g/defmolmass.htm molecular weight molecular weights molecular mass mass MOL WEIGHT A number equal to the sum of the atomic masses of the atoms in a molecule. The molecular mass gives the mass of a molecule relative to that of the 12C atom, which is taken to have a mass of 12. Ontology1271664172453:molecular_weight_and_average_atomic_weight http://www.codessa-pro.com/descriptors/const.htm molecular weight and average atomic weight Ontology1271664172453:monovalent_cooperative_binding_ monovalent cooperative binding monovalent binding Ontology1271664172453:mouth_size mouth size Ontology1271664172453:native_conformation http://www.biology-online.org/dictionary/Native_conformation native conformation native conformations The conformation in which a molecule is biologically active. Ontology1271664172453:necessary_binding_site protein-protein interaction ontology http://bioportal.bioontology.org/visualize/39508 necessary binding site necessary binding sites required to bind A sequence range within a protein identified as being absolutely required for an interaction. Ontology1271664172453:negative_allosteric_modulator http://en.wikipedia.org/wiki/Negative_allosteric_modulator negative allosteric modulator negative allosteric modulators NAM A negative allosteric modulator (NAM) is a drug which decreases the activity of a receptor indirectly via disactivation of an allosteric site on the protein. NAMs are similar to inverse agonists in that they conteract overall receptor activation, but they are different due to the fact that they do so in a functionally distinctive way. Ontology1271664172453:negative_cooperativity http://www.nature.com/nrd/journal/v1/n10/glossary/nrd917_glossary.html http://science.jrank.org/pages/27658/cooperative-ligand-binding.html negative cooperativity negative cooperativities negative cooperative binding interaction negatively cooperative binding negative binding cooperativity A property of a multi-site-binding protein (for example an enzyme or a receptor) whereby the binding of one ligand molecule decreases the binding affinity of other ligand molecules to neighbouring binding sites. The binding of one ligand molecule to one site decreases (negative cooperativity) the affinity of the other site(s) for ligand(s). Ontology1271664172453:negative_electrostatic_potential negative electrostatic potential negative electrostatic potentials electronegative potential electronegative potentials Ontology1271664172453:non-polar_surface_area non-polar surface area Non-polar Surface Area - is the sum of surface contributions of non-polar atoms. Ontology1271664172453:nonspecific_binding http://www.graphpad.com/curvefit/nonspecific_binding.htm nonspecific binding non-specific binding Nonspecific binding - binding to the site (receptors, transporters, ect) not of interest to the investigator. Ontology1271664172453:optical_isomer http://goldbook.iupac.org/O04308.html optical isomer optical isomers Obsolescent synonym for stereoisomers with different optical properties. They should be described as diastereoisomers or enantiomers. Ontology1271664172453:orthosteric_site http://www.reportbuyer.com/samples/c37bead2a8f831492fcaa97028cb9b76.pdf orthosteric site orthosteric sites primary site The primary binding site on the receptor that is regognized by the endogenous agonist for that receptor. Ontology1271664172453:pA2 http://pharmrev.aspetjournals.org/content/55/4/597/T4.expansion pA2 The negative logarithm to base 10 of the molar concentration of an antagonist that makes it necessary to double the concentration of the agonist needed to elicit the original submaximal response obtained in the absence of antagonist (Schild, 1947, 1949). Ontology1271664172453:pEC50 pEC50 p[A]50 The negative logarithm to base 10 of the EC50 of an agonist. Ontology1271664172453:pK http://antoine.frostburg.edu/chem/senese/101/acidbase/faq/what-is-pH.shtml pK pK(i) pH = -log[H+] where log is a base-10 logarithm and [H+] is the concentration of hydrogen ions in moles per liter of solution. H++ is an automated system that computes pK values of ionizable groups in macromolecules and adds missing hydrogen atoms according to the specified pH of the environment. Given a (PDB) structure file on input, H++ outputs the completed structure in several common formats (PDB, PQR, AMBER inpcrd/prmtop) and provides a set of tools useful for analysis of electrostatic-related molecular properties. link: http://biophysics.cs.vt.edu/H++/index.php pH is a logarithmic measure of hydrogen ion concentration Ontology1271664172453:pKa http://www.vcclab.org/lab/alogps/start.html Pka Pk(a) Pk(a The strength of an acid can be determined by considering the extent to which it dissociates in a given solvent (i.e. to which side this equilibrium lies): H2O+HX⇔ (H3O+) +X- The equilibrium constant in water is given by: Ka=([H3O+] [X-])/ [HX] Ka is known as the acidity constant of the acid. Its value will only be approximate if concentrations are used as shown above; strictly the activities of the species involved should be used. However, using concentrations will be fairly accurate provided the solution is dilute. Generally, the numerical value of Ka will be small, and for this reason, Ka is usually converted into pKa by the following equation: pKa=-ln[Ka] pKa = 3.77 Thus, the smaller the value of pKa, the stronger the acid. Acid: a substance that can donate a proton Base: a substance that can accept a proton PDB2PQR -- An automated pipeline for the setup, execution, and analysis of Poisson-Boltzmann electrostatics calculations. PDB2PQR is a Python software package that automates many of the common tasks of preparing structures for continuum electrostatics calculations, providing a platform-independent utility for converting protein files in PDB format to PQR format. These tasks include: - Adding a limited number of missing heavy atoms to biomolecular structures -Determining side-chain pKas -Placing missing hydrogens -Optimizing the protein for favorable hydrogen bonding - Assigning charge and radius parameters from a variety of force fields link: http://www.poissonboltzmann.org/pdb2pqr PDB2PQR uses PROPKA to determine protein pKa values. PROPKA is developed by the Jensen Research Group at the University of Copenhagen. More information about PROPKA can be found at http://propka.ki.ku.dk/. Software For Protein pKa Calculations: AccelrysPKA Accelrys CHARMm based pKa calculation H++ Poisson-Boltzmann based pKa calculations MCCE Multi-Conformation Continuum Electrostatics Karlsberg+ pKa computation with multiple pH adapted conformations. pKD server pKa calculations and pKa value re-design PROPKA Empirical calculation of pKa values http://en.wikipedia.org/wiki/Protein_pKa_calculations#Software_For_Protein_pKa_Calculations The strength of an acid can be determined by considering the extent to which it dissociates in a given solvent (i.e. to which side this equilibrium lies): H2O+HX <-> (H3O+) +X- The equilibrium constant in water is given by: Ka=([H3O+] [X-])/ [HX] Ka is known as the acidity constant of the acid. Its value will only be approximate if concentrations are used as shown above; strictly the activities of the species involved should be used. However, using concentrations will be fairly accurate provided the solution is dilute. Generally, the numerical value of Ka will be small, and for this reason, Ka is usually converted into pKa by the following equation: pKa=-ln[Ka] Acid: a substance that can donate a proton Base: a substance that can accept a proton Ontology1271664172453:pKb http://www.everyscience.com/Chemistry/Organic/Acids_and_Bases/b.1173.php pKb pK(b) pK(B) affinity constant Base dissociation constant The strength of a base is determined by using pKb. For the example of BOH, a base, in water, Kb can be determined by the following formula: Kb=[B+][OH-]/[BOH] pKb=-ln[Kb] The strength of a base is determined by using pKb. For the example of BOH, a base, in water, Kb can be determined by the following formula: Kb=[B+][OH-]/[BOH] pKb=-ln[Kb] Ontology1271664172453:pKi pKi=-ln[Ki] Ontology1271664172453:partial_agonist http://pharmrev.aspetjournals.org/content/55/4/597/T6.expansion partial agonist partial agonists partial agonism An agonist that in a given tissue, under specified conditions, cannot elicit as large an effect (even when applied at high concentration, so that all the receptors should be occupied) as can another agonist acting through the same receptors in the same tissue. Ontology1271664172453:permeability http://en.wiktionary.org/wiki/permeability permeability permeabilities The property of being permeable The rate of flow of a fluid through a porous material Ontology1271664172453:pharmacological_antagonist pharmacological antagonist pharmacological antagonists Ontology1271664172453:pharmacophore_descriptors C.G Wermuth, et al., Glossary of terms used in medicinal chemistry (IUPAC Recommendations 1998). Pure Appl. Chem., 1998. 70(5): p. 1129-1143. Taboureau, O., 3D descriptors and fingerprints, Chemoinformatics, CBS-BioCentrum. pharmacophore descriptor pharmacophore descriptors ph4 descriptor ph4 descriptors pharmacophore feature pharmacophore features pharmacophoric points pharmacophoric point pharmacophoric feature pharmacophoric features 1) Pharmacophoric descriptors are used to define a pharmacophore, including H-bonding, hydrophobic and electrostatic interaction sites, defined by atoms, ring centers and virtual points. 2) Pharmacophore descriptors are pharmacophore points - points in molecule likely to be involved in binding to a receptor site: • positive charges • negative charges • hydrogen-bond donors (e.g. –OH, – NH2) • hydrogen-bond acceptors (e.g. =O) • aromatic groups • hydrophobic groups Pharmacophoric points do not necessarily coincide with the positions of individual atoms. Ontology1271664172453:pharmacophore_fingerprint Taboureau, O., 3D descriptors and fingerprints, Chemoinformatics, CBS-BioCentrum. pharmacophore fingerprint pharmacophore fingerprints pharmacophoric fingerprint pharmacophoric fingerprints A pharmacophore is the ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target structure and to trigger (or to block) its biological response. Distance between the features are taking account. 2D and 3D pharmacophore fingerprint are possible. Pharmacophore fingerprint: each fragment consists of 3 pharmacophoric points – the distances between each pair of these points are binned and used toset fingerprint bits 4-point pharmacophore fragments are also used Main advantage is that it takes account the conformational flexibility and chirality which can be also is main weakness. Ontology1271664172453:physicochemical_properties http://www.thefreedictionary.com/physicochemical physicochemical property physicochemical properties physico-chemical property physico-chemical properties physico-chemical binding site property physico-chemical binding site properties Physicochemical properties are concerned with, or relating to physical chemistry or both physics and chemistry. Ontology1271664172453:physiological_agonist http://en.wikipedia.org/wiki/Agonist physiological agonist physiological agonists A physiological agonist is a substance that creates the same bodily responses but does not bind to the same receptor. Ontology1271664172453:physiological_antagonism http://pharmrev.aspetjournals.org/content/55/4/597/T1.expansion physiological antagonism physiological antagonism in which the action of one agonist exerts an opposite effect to that of the original agonist—usually through a different receptor (e.g., muscarinic agonist inhibition of β adrenoceptor-stimulated adenylyl cyclase activity in the heart). Ontology1271664172453:place_and_join MOE:http://www.chemcomp.com/software.htm place and join place and join algorithm The place-and-join method is based on the additivity hypothesis of atomic interactions between a protein and a small molecule, which allows local regions to be treated independently. The intial molecule is then regenerated by assembling the elementary docked fragments.The main difficulty of the method is that many placements are generated for each individual fragment, so that going over all the possibilities in order to select best scoring feasible assemblies is computationally expensive; this requires efficient management of individual docked solutions. Ontology1271664172453:pocket_volume pocket volume volume of pocket Ontology1271664172453:polyspecificity polyspecificity polyspecificities polyspecific Ontology1271664172453:polyvalent_cooperative_binding polyvalent cooperative binding polyvalent binding Ontology1271664172453:positive_cooperativity http://www.curvefit.com/allosteric_enzymes.htm http://science.jrank.org/pages/27658/cooperative-ligand-binding.html positive cooperativity positive cooperativities positively cooperative binding positive binding cooperativity If binding of substrate to one binding site increases the activity of neighboring sites, the term positive cooperativity is used. The binding of one ligand molecule to one site increases (positive cooperativity) the affinity of the other site(s) for ligand(s). Ontology1271664172453:positive_electrostatic_potential positive electrostatic potential positive electrostatic potentials Ontology1271664172453:protein http://antoine.frostburg.edu/chem/senese/101/glossary/p.shtml Xie, L., et al., Knowledge Discovery of Protein-Ligand Interaction Network, in Conference on Semantics in Healthcare and Life Sciences (CSHALS). 2010: Cambridge/Boston, MA. Protein Proteins gene product A complex polymer made by linking together amino acid molecules. Proteins sometimes contain non-amino acid components such as metal ions or porphyrin rings embedded within. Ontology1271664172453:protein_type protein type protein types Ontology1271664172453:protrusion http://www.thefreedictionary.com/protrusion protrusion protrusions The state of being protruded. Ontology1271664172453:quantitative_structure-affinity_relationship quantitative structure-affinity relationship quantitative structure-affinity relationships quantitative structure-affinity relationship approach Ontology1271664172453:reaction_ability http://chemistry.about.com/od/engineeringglossary/g/chemical-reaction-definition.htm reaction ability reaction abilities reactive reactivity Ability of a compound to participate in chemical reaction.A chemical reaction is a chemical change which forms new substances. Ontology1271664172453:recognition_site http://goldbook.iupac.org/R05199.html recognition site recognition sites site of recognition 1. A nucleotide sequence to which a protein binds specifically. 2. An amino acid sequence in an antibody molecule to which the specific antigen binds specifically. Ontology1271664172453:redocking http://autodock.scripps.edu/faqs-help/glossary/redocking redocking redockings re-docking self-docking self-dockings The process by which a ligand taken from the structure of a complex of it with a receptor, and docked to the "induced-fit" form of the receptor. This is often performed to verify that the docking parameters specified in the input file for the docking method are reasonable, and able to recover a known complex's structure and interactions. Ontology1271664172453:reversible_competitive_antagonism Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. reversible competitive antagonism reversible competitive antagonist If the agonist and antagonist form only short-lasting combinations with the receptor, so that equilibrium between agonist, antagonist, and receptors is reached during the presence of the agonist, the antagonism will be surmountable over a wide range of concentrations Ontology1271664172453:reversible_inhibitor reversible inhibitor reversible inhibitors have to possess high affinity binding to the enzyme for inhibition, binding via (cleavable) chemical linkages. Ontology1271664172453:rigid_combining_site Zimmermann, J., et al., Molecular description of flexibility in an antibody combining site. J Phys Chem B, 2010. 114(21): p. 7359-70 Rigid combining site Rigid combining sites Rigid combining site is a combining site which is locked into a conformation which is specific for a given antigen. Ontology1271664172453:rotamer http://goldbook.iupac.org/R05407.html rotamer rotamers rotameric conformers One of a set of conformers arising from restricted rotation about one single bond. Ontology1271664172453:rotational_entropy http://www.codessa-pro.com/descriptors/thermodynamic/index.htm http://www.codessa-pro.com/descriptors/thermodynamic/rem.htm rotational entropy rotational entropies Rotational entropy of the molecule: Srot=Nk*ln[((π1/2)/σ)Π((8(π2)*Ij*K*T)/(h2))1/2] The product Π in this formula is started from j=1 till 3 (π1/2) means that π is in the power of 1/2 (π2) means that π is in the power of 2 (h2) means that h is in the power of 2 ((8(π2)*Ii*K*T)/(h2))1/2 means that ((8(π2)*Ii*K*T)/(h2)) is in the power of 1/2 Ij - principal moments of inertia of the molecule σ - symmetry number of the molecule h - Planck's constant k - Boltzmann's constant T - absolute temperature (K Ontology1271664172453:rugged_activity_landscape Peltason, L., et al., Exploration of structure-activity relationship determinants in analogue series. J Med Chem, 2009. 52(10): p. 3212-24. rugged activity landscape rugged activity landscapes rugged landscapes rugged landscape If changes in molecular structure result in substantial changes in potency, the resulting landscapes are rugged and include activity cliffs. Ontology1271664172453:saddle_point http://www.shodor.org/chemviz/glossary.html http://mathworld.wolfram.com/SaddlePoint.html Minkin, V.I., Glossary of terms used in theoretical organic chemistry. Pure Appl. Chem, 1999. 71(10): p. 1919-1981. saddle point saddle points saddle point region saddle point regions A molecular geometry such that slight changes cause both a maximum in one direction and a minimum in the other. Saddle points represent a transition structure connecting two equilibrium structures. Mathematical definition: A point of a function or surface which is a stationary point but not an extremum.Surfaces can also have saddle points, which the second derivative test can sometimes be used to identify. Examples of surfaces with a saddle point include the handkerchief surface and monkey saddle. Saddle point - A point of lowest maximum energy on a valley (reaction path) connecting two minima on the potential energy surface. In mathematical terms, the stationary point on the PES in which the Hessian matrix has only one negative eigenvalue is assigned to the saddle point of the first rank. The saddle point is associated with the transition state structure. Ontology1271664172453:scoring I.Halperin, B.Ma, H.Wolfson, and R.Nussinov. Principles of docking: An overview of search algorithms and a guide to scoring functions. Proteins: Structure, Function and Genetics, 2002. scoring contact scoring docking score docking scores score scores interaction energy scoring Prediction of the free energy of binding of a small molecule ligand based on the given 3D structure of a protein ligand complex. Ontology1271664172453:scoring_function http://en.wikipedia.org/wiki/Scoring_functions_for_docking scoring function scoring functions fitness function docking functions docking function Scoring fuction access the quality of a particular pose by counting the number of favorable intermolecular interactions such as hydrogen bonds and hydrophobic contacts, ect. Pose – A candidate binding mode. Ontology1271664172453:scoring_problems http://www.cs.cmu.edu/~blmt/Seminar/SeminarMaterials/interactions.html scoring problem scoring problems problems of scoring Problems: - assumption that free energy of binding is dominated by a single mode - solvation effects difficult to quantify - conformational changes of protein difficult to quantify - loss of entropy during complex formation difficult to quantify Ontology1271664172453:selected-fit_model Weikl, T.R. and C. von Deuster, Selected-fit versus induced-fit protein binding: kinetic differences and mutational analysis. Proteins, 2009. 75(1): p. 104-10. selected-fit model selected-fit models selected-fit mechanism selected-fit binding selected-fit process The selected-fit mechanism corresponds to ligand binding in the excited state to the receptor. Ontology1271664172453:selective_agonist Kenakin, T., Inverse, protean, and ligand-selective agonism: matters of receptor conformation. FASEB J, 2001. 15(3): p. 598-611. Urban, J.D., et al., Functional selectivity and classical concepts of quantitative pharmacology. J Pharmacol Exp Ther, 2007. 320(1): p. 1-13. Smith, C.L. and B.W. O'Malley, Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr Rev, 2004. 25(1): p. 45-71. selective agonist selective agonists receptor-selective agonist receptor-selective agonists A selective agonist is selective for one certain type of receptor. It can be of any of the aforementioned types. New findings that broaden the conventional definition of pharmacology demonstrate that ligands can concurrently behave as agonist and antagonists at the same receptor, depending on effector pathways or tissue type. Terms that describe this phenomenon are "functional selectivity", "protean agonism", or selective receptor modulators. Ontology1271664172453:selective_antagonist selective antagonist selective antagonists receptor-selective antagonist receptor-selective antagonists subtype selective antagonist subtype selective antagonists Ontology1271664172453:selectivity selectivity selectivities target selectivity ligand selectivity receptor subtype-selectivity tissue selectivity receptor selectivity target-site selectivity sub-type selectivity subtype-selectivity Ontology1271664172453:selectivity_cliff Hu, Y. and J. Bajorath, Molecular scaffolds with high propensity to form multi-target activity cliffs. J Chem Inf Model, 2010. 50(4): p. 500-10. selectivity cliffs selectivity cliffs Selectivity cliffs can be defined that are formed by structural analogs having significantly different potencies against two targets. Ontology1271664172453:simulated_annealing MOE:http://www.chemcomp.com/software.htm simulated annealing Montecarlo-simulated annealing simulated annealing protocols CSA SA simulated annealing calculations simulated annealing procedure simulated annealing simulations simulated annealing optimization procedure simulated annealing methods simulated annealing algorithm simulated annealing-based algorithm programme example: ICM, DOCK Simulated annealing is a technique derived from Monte Carlo methods where the system is heated and then cooled slowly. Heating allows the system to cross energy barriers and visit the whole conformational surface. Cooling drives the system into energy minimum. This process is generally repeated many times until several very closely related and low energy solutions are obtained. The configuration of the lowest energy is assumed to be the exact docked solution. Ontology1271664172453:simulation_method simulation method simulation methods simulation approach simulation modeling simulations molecular simulations Simulation procedures programme example : ICM, DOCK Ontology1271664172453:smooth_activity_landscape Peltason, L., et al., Exploration of structure-activity relationship determinants in analogue series. J Med Chem, 2009. 52(10): p. 3212-24 smooth activity landscape smooth activity landscapes If progressive changes in compound structure only have small to moderate effects on biological activity, smooth activity landscapes are observed. Ontology1271664172453:solubility http://chemistry-dictionary.com/definition/solubility.html http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI solubility solubilities Solubility Calculator: 1) http://michele.usc.edu/java/solubility/solubilityinst.html 2)http://chemmac1.usc.edu/bruno/java/solub.html Solubility prediction This Applet provides interactive on-line prediction of logP, water solubility and pKa(s) of compounds for drug design (ADME/T and HTS) and environmental chemistry studies. http://www.vcclab.org/lab/alogps/ http://www.vcclab.org/lab/alogps/start.html Solubility is the amount of a solute that will dissolve in a specific solvent under given conditions. The dissolved substance is called the solute and the dissolving fluid (usually present in excess) is called the solvent, which together form a solution. The process of dissolving is called solvation, or hydration if the solvent is water. Potential ability of a substance to dissolve in a liquid. Ontology1271664172453:solvation_free_energy solvation free energy solvation free energies ΔG(solvation)=ΔG(electrostatic)+ΔG(Van Der Waals)+ΔG(cavity) Program ChemSol is designed for the calculations of solvation free energies using the Langevin Dipoles (LD) solvation model, in which the solvent is approximated by polarizable dipoles fixed on a cubic grid. link: http://futura.usc.edu/programs/chemsol/ online calculation : http://futura.usc.edu/programs/chemsol/cs-1.0/index.html Ontology1271664172453:solvent-excluded_volume http://www.netsci.org/Science/Compchem/feature14e.html solvent-excluded volume solvent-excluded volumes SEV The term solvent-excluded volume to mean the volume enclosed by the molecular surface. It is the volume that the probe sphere is excluded from. Ontology1271664172453:solvent_accessible_surface_area http://boscoh.com/protein/calculating-the-solvent-accessible-surface-area-asa solvent accessible surface area solvent accessible surface areas solvent accessible surface SAS ASA SASA The Solvent Accessible Surface of a molecule is the part of the molecular surface that is exposed to the solvent and is accessible to the solvent. Ontology1271664172453:specific_binding http://www.graphpad.com/curvefit/nonspecific_binding.htm specific binding domain specific binding specific binding = total binding - nonspecific binding Ligand binding to the receptor of interest is called specific binding. Ontology1271664172453:stereoisomer http://goldbook.iupac.org/S05984.html stereoisomer stereiosomers stereoisomeric Stereoisomerism Isomers that possess identical constitution, but which differ in the arrangement of their atoms in space. Ontology1271664172453:stretching_interaction_energy Kholodovych, V., Molecular Mechanics, University of Medicine&Dentistry of New Jersey (UMDN J). stretching interaction energy stretching interaction energies stretching energy energy of stretching stretching Hooke's law: E=Σk(r-ro)2 ((r-ro)2 means r in the power of two) Σ-sum over the bonds F- force k- controls the stiffness of the bond spring r- bond length after stretching ro - equilibrium bond length E- estimates energy associated with vibration about equilibrium bond length. Energy accosiated with vibration around equilibrium bond length based on the Hook's law. Ontology1271664172453:structural_interaction_fingerprint Deng, Z., C. Chuaqui, and J. Singh, Structural interaction fingerprint (SIFt): a novel method for analyzing three-dimensional protein-ligand binding interactions. J Med Chem, 2004. 47(2): p. 337-44. structural interaction fingerprint structural interaction fingerprints SIF SIFt protein-ligand interaction fingerprint protein-ligand interaction fingerprints Interaction fingerprint that translates 3D structural binding information from a protein-ligand complex into a one-dimensional binary string. Each fingerprint represents the "structural interaction profile" of the complex that can be used to organize, analyze, and visualize the rich amount of information encoded in ligand-receptor complexes and also to assist database mining. Ontology1271664172453:structure_based_prediction Protein-protein interaction Ontology http://bioportal.bioontology.org/visualize/39508 structure based prediction structure based predictions predict from struct Methods based on 3D structure information. Ontology1271664172453:sufficient_binding_site protein-protein interaction ontology http://bioportal.bioontology.org/visualize/39508 sufficient binding site sufficient binding sites sufficient to bind Binding will occur when this sequence range is present within a protein. Ontology1271664172453:superagonist http://en.wikipedia.org/wiki/Agonist superagonist superagonists A superagonist is a compound that is capable of producing a greater maximal response than the endogenous agonist for the target receptor, and thus has an efficacy of more than 100%. This does not necessarily mean that it is more potent than the endogenous agonist, but is rather a comparison of the maximum possible response that can be produced inside the cell following receptor binding. Ontology1271664172453:surface_area http://www.math.com/tables/geometry/surfareas.htm surface area surface areas SA The surface area is the sum of all the areas of all the shapes that cover the surface of the object. Ontology1271664172453:surface_cavity Liu, Z.P., et al., Protein cavity clustering based on community structure of pocket similarity network. Int J Bioinform Res Appl, 2008. 4(4): p. 445-60. surface cavity surface cavities clefts pocket pockets cleft Surface cavities are ordinarily regarded as potentially active sites where the protein carries out the functions. Ontology1271664172453:surface_plasmon_resonance http://medical.webends.com/kw/Surface%20Plasmon%20Resonance surface plasmon resonance SPR plasmon resonance A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. Ontology1271664172453:surface_property surface property surface properties Property of a surface Ontology1271664172453:surmountable_antagonism Neubig, R.R., et al., International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacol Rev, 2003. 55(4): p. 597-606. surmountable antagonism surmountable antagonist surmountable antagonists Surmountable antagonism is generally observed with reversible competitive antagonism though it may also occur with chemical antagonism, with irreversible antagonists in the case of spare receptors, or with certain forms of allosteric antagonism. If the agonist and antagonist form only short-lasting combinations with the receptor, so that equilibrium between agonist, antagonist, and receptors is reached during the presence of the agonist, the antagonism will be surmountable over a wide range of concentrations. Ontology1271664172453:systematic_search MOE:http://www.chemcomp.com/software.htm Kholodovych, V., Molecular Mechanics, University of Medicine&Dentistry of New Jersey (UMDN J). systematic search systematic conformation search systematic sampling systematic search method systematic orientational search Systematic conformation search generates molecular conformations by systematically rotating bonds in the molecule by discrete increments. The purpose is to generate a collection of reasonable molecular conformations, which may or may not be at local minima. Advantage: Explore all conformational space systematically. All possible minimal conformers can be found. Disadvantage: Time consuming: combinatorial explosion. Can not be used for large system and has a great limitation for ring systems. Ontology1271664172453:text_mining Protein-protein interaction ontology http://bioportal.bioontology.org/visualize/3950 text mining Text mining methods can be used to predict or confirm interactions by automated processing of scientific literature. Co-occurrence in the same sentence of an abstract of gene products labels are analysed to evaluate whether it represents a valid evidence of an interaction. Ontology1271664172453:three_point_pharmacophore_fingerprint Taboureau, O., 3D descriptors and fingerprints, Chemoinformatics, CBS-BioCentrum. three point pharmacophore fingerprint three point pharmacophore fingerprints 3 point pharmacophore fingerprint 3 point pharmacophore fingerprints Each fragment consists of 3 pharmacophoric points. – the distances between each pair of these points are binned and used to set fingerprint bits. Ontology1271664172453:torsion_energy Kholodovych, V., Molecular Mechanics, University of Medicine&Dentistry of New Jersey (UMDN J). http://rumour.biology.gatech.edu/YammpWeb/techdoc/energy/torsions/intro.shtml torsion energy torsion energies torsion energy: E=ΣA[1+cos(nτ-Φ)] Σ - sum over torsions τ-torsion angle spanned by atoms i, k ,j, l Φ - phase shift n - periodicity A - reference energy E - torsion energy Torsion energy due to twisting around bonds. Ontology1271664172453:total_and_relative_number_of_6-atoms_aromatic_rings http://www.codessa-pro.com/descriptors/const.htm total and relative number of 6-atoms aromatic rings Ontology1271664172453:total_number_of_atoms http://www.codessa-pro.com/descriptors/const.htm total number of atoms total number of atoms in the molecule Ontology1271664172453:total_number_of_bonds http://www.codessa-pro.com/descriptors/const.htm total number of bonds total number of bonds in the molecule Ontology1271664172453:translational_entropy translational entropy translational entropies Translational entropy of the molecule: Str=ln(((2πmKT)/(h2))1/2)* ((Ve5/2)/Na) ((2πmKT)/(h2))1/2 means that ((2πmKT)/(h2)) is in the power of 1/2 e5/2 means that e is in the power of 5/2 h2 means h is in the power of 2 V - volume of the system NA - Avogadro's number m - mass of the molecule h - Planck's constant k - Boltzmann's constant T - absolute temperature (K) Ontology1271664172453:viscosity http://www.princeton.edu/~gasdyn/Research/T-C_Research_Folder/Viscosity_def.html viscosity viscosities Visc Viscosity is a measure of a fluid's resistance to flow. It describes the internal friction of a moving fluid. A fluidwith large viscosity resists motion because its molecular makeup gives it a lot of internal friction. A fluid with low viscosity flows easily because its molecular makeup results in very little friction when it is in motion. Ontology1271664172453:volume_property volume property volume properties Property of a volume. Ontology12716641724532:D-QSAR http://www.chem.qmul.ac.uk/iupac/medchem/ix.html#t2 3D-QSAR 3D-QSARs three-dimensional quantitative structure-activity relationship three-dimensional quantitative structure-activity relationships three-dimensional QSAR three-dimensional QSARs A three-dimensional quantitative structure-activity relationship is the analysis of the quantitative relationship between the biological activity of a set of compounds and their spatial properties using statistical methods. most_positive:_atomic_partial_charges http://www.codessa-pro.com/descriptors/electrostatic/npc.htm Minimum (most negative) and maximum (most positive) atomic partial charges Qmin =min (Q -) Qmax=max (Q+) Q - negative atomic partial charges Q+ positive atomic partial charges Surface:volume_properties surface/volume property surface/volume properties vis:_absorption_spectroscopy_ Nienhaus, K. and G.U. Nienhaus, Probing heme protein-ligand interactions by UV/visible absorption spectroscopy. Methods Mol Biol, 2005. 305: p. 215-42. Ultraviolet/visible (UV/vis) absorption spectroscopy (UV/vis) absorption spectroscopy UV-vis absorption spectroscopy UV/vis absorption spectroscopy UV/visible absorption spectroscopy UV-visible absorption spectroscopy Ultraviolet/visible (UV/vis) absorption spectroscopy is a powerful tool for steady-state and time-resolved studies of protein-ligand interactions. Prosthetic groups in proteins frequently have strong electronic absorbance bands that depend on the oxidation, ligation, and conformation states of the chromophores. They are also sensitive to conformational changes of the polypeptide chain into which they are embedded. Steady-state absorption spectroscopy provides information on ligand binding equilibria, from which the Gibbs free energy differences between the ligated and unligated states can be computed. Time-resolved absorption spectroscopy allows one to detect short-lived intermediate states that may not get populated significantly under equilibrium conditions, but may nevertheless be of crucial importance for biological function. Moreover, the energy barriers that have to be surmounted in the reaction can be determined. http://www.codessa-pro.com/descriptors/const.htm absolute and relative numbers of atoms of certain chemical identity (C, H, O, N, F, etc.) absolute and relative numbers of atoms of certain chemical identity (C, H, O, N, F, etc.) in the molecule _triple:_aromatic_or_other_bonds http://www.codessa-pro.com/descriptors/const.htm absolute and relative numbers of single, double, triple, aromatic or other bonds absolute and relative numbers of single, double, triple, aromatic or other bonds in the molecule hybrid_QM:MM_molecular_dynamics_simulation Webb, B., overview of hybrid QM/MM methods, University of California: San Francisco. http://goldbook.iupac.org/QT07469.html hybrid OM/MM molecular dynamics simulation hybrid OM/MM molecular dynamics simulations QM/MM QM/MM approach hybrid QM/MM methods combined quantum mechanics/molecular mechanics combined quantum mechanics/ molecular mechanics simulations quantum mechanics/molecular mechanics hybrid QM/MM Hamiltonian: Htotal = H(QM) + H(MM) + H(QM/MM) Htotal - total Hamiltonian H(QM) - Hamiltonian which describes part of the ststem which is treated quantum mechanically (QM) where the reaction under goes. H(MM) - Hamiltonian which describes part of the ststem which is treated molecular mechanically (MM) (surroundings). H(QM/MM) - Hamiltonian which describes part of the ststem which is treated molecular mechanically and quantum mechanically (QM/MM). Combines quantum mechanical and molecular mechanical methods. Treats just the reacting part of the system quantum mechanically, and uses MM (molecular mechanics) for the surroundings. Hybrid procedure for the treatment of large molecular systems. A crucial part of the system (e.g., the chromophore and its surroundings) is treated explicitly by quantum mechanical (QM) techniques, whereas the rest of the system is approximated by a classical or molecular mechanics (MM) force field treatment. stochastic:random_search MOE:http://www.chemcomp.com/software.htm stochastic/random search random search random sampling stochastic process Stochastic optimization methods SO stochastic torsional searches Stochastic search methods modify the conformation of the small molecule (randomly) in the receptor site and assess it on the fly. total_number_of_rings:_number_of_rings_divided_by_the_total_number_of_atoms http://www.codessa-pro.com/descriptors/const.htm total number of rings, number of rings divided by the total number of atoms owl:Thing