SCORING FUNCTION PENALIZING COMPOUNDS WHICH DESOLVATE CHARGED PROTEIN SIDE CHAINS STRUCTURE

摘要

A method of scoring binding affinity of a proposed ligand molecule for a receptor molecule using a computer and computer data bases, which accounts for the increase in energy required where docking disrupts water molecules that are localized or localized. The method uses computer-stored data representing a predicted ligand-receptor structure (preferably one that is validated) as well as computer-stored data representing a library of compounds to be tested. Data representing members of the compound library is analyzed by computerized operations which determine whether the receptor in the predicted ligand-receptor structure includes a) determining whether the receptor in the predicted ligand-receptor structure includes solvating water molecule(s) whose desovlation into the surrounding environment requires substantial energy, b) determining whether a docking configuration for a member of the compound library with the receptor requires desolvation of one or more of the desolvating water molecule(s).