Binding affinity scoring function penalizing compounds which make unfavorable hydrophobic contacts with localized water molecules in the receptor active site

Abstract

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 at ligand hydration sites. The method uses computer-stored data representing a predicted ligand-receptor structure (preferably one that is validated). The computerized scoring analysis includes determining whether the receptor includes one or more hydration sites occupied by localized water, and, if so, assessing a penalty if docking the ligand into the receptor results in unfavorable interaction of the ligand with a localized water molecule remaining at the receptor hydration site (i.e. after docking).