Binding affinity scoring with penalty for breaking conjugation between aromatic ligand groups

Abstract

A method of scoring binding affinity of a proposed ligand molecule for a receptor molecule using computer analysis and computer data bases to accounts for the increase in energy required where docking disrupts or partially disrupts the π-conjugated character of the ligand when bound to the receptor. The method uses data representing one or more proposed ligand molecules to be scored and data representing the receptor molecule. Computer analysis of the proposed ligand molecule data determines whether the ligand includes at least one π-conjugated moiety having multiple possible geometries, one of those geometries being characterized by less delocalization of electrons across the π-conjugated moiety than the delocalization of electrons characterizing another of those geometries. Computer analysis of the predicted ligand-receptor structure determines whether the ligand in the ligand-receptor structure adopts the geometry characterized by less delocalization. If so, a penalty is explicitly imposed for reduced delocalization of electrons across the π-conjugated moieties.