METHOD modeling and prediction of binding ligand molecules to a target molecule methods of quantum mechanics with the influence of Solvent

摘要

FIELD: pharmaceutics.;SUBSTANCE: method includes building models of inter-molecular complex and its components, using data concerning composition of target molecule and ligand molecule. Models for apparent and implicit flow count of solvent are introduced. Modeling of connection of ligand molecule and target molecule with consideration of solvent effect is performed either within limits of quantum-mechanical, or within limits of combined quantum-mechanical and classic approaches. Calculation of enthalpy of connection of target molecule and ligand molecule is performed, using full energies of molecular systems, calculated at minimal point or using average values of full energies, produced for a set of configurations of inter-molecular complex of target-ligands. In latter case, coordinates of atoms of target molecule, ligand molecule and their inter-molecular complex, appropriate for each of such configurations, are produced within limits of molecular-dynamic modeling. Calculation of entropy of connection of ligand molecule and target molecule is performed on basis of calculation of its oscillation, rotation and linear components. Free energy of connection of ligand molecule and target molecule is made on basis of enthalpy, entropy member and cavitation energy.;EFFECT: production at given precision level of energy values, characterizing intensiveness of connection of receptor and remedy, and, consecutively, are a criterion during predicting ligands as potential remedial substances.;3 cl, 9 dwg, 2 tbl