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 ?-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 ?-conjugated moiety having multiple possible geometries, one of those geometries being characterized by less delocalization of electrons across the ?-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.

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).

Abstract: A computer-implemented method for calculating a value representative of interaction (VRI) of a proposed ligand with a specified receptor. Hydrophobic interactions between one or more ligand atoms and one or more receptor atoms are scored by a method that awards a bonus for the presence of hydrophobic enclosure of one or more ligand atoms by the receptor. Also, charge-charge hydrogen bonds between a ligand and a receptor are scored by setting a default value for a charge-charge hydrogen bond and awarding a bonus above the default value when one or more specialized predetermined charge-charge hydrogen bond criteria is satisfied. Various charge-charge hydrogen bond criteria are used. Zwitterions, charge, salvation, geometry and electrostatic energy are accounted for.