A computer-implemented method of scoring binding affinity of a proposed ligand molecule for a known receptor, which is a protein, which method uses a computer and computer stored data, the method comprising, a. receiving, by one or more computers, data representing one or more proposed ligand molecules to be scored, b. receiving, by one or more computers, data representing a predicted structure of a complex between a receptor and the proposed ligand molecule, c. scoring the proposed ligand binding affinity by a method comprising using the data of a. and b. in i. computer analysis of the proposed ligand molecule data to determine whether the ligand includes at least one π-conjugated moiety having multiple possible geometries, one of the geometries being characterized by less delocalization of electrons across the π-conjugated moiety than the delocalization of electrons characterizing another of the geometries, ii. computer analysis of the predicted ligand-receptor structure which includes determining whether the ligand in the ligand-receptor structure adopts the geometry characterized by less delocalization, iii. if so, including in the scoring a penalty for reduced delocalization of electrons across the π-conjugated moieties, wherein the magnitude of the penalty is an amount reflecting the reduction of electron delocalization between the configuration of the proposed ligand when complexed with the receptor and the delocalization of an uncomplexed, more delocalized, configuration of the proposed ligand, in which step c. i. includes determining whether the ligand includes one or more rotatable bond paths connecting two chemical moieties which are capable of significant π electron delocalization between the groups across the rotatable bond. a. receiving, by one or more computers, data representing one or more proposed ligand molecules to be scored, b. receiving, by one or more computers, data representing a predicted structure of a complex between a receptor and the proposed ligand molecule, c. scoring the proposed ligand binding affinity by a method comprising using the data of a. and b. in i. computer analysis of the proposed ligand molecule data to determine whether the ligand includes at least one π-conjugated moiety having multiple possible geometries, one of the geometries being characterized by less delocalization of electrons across the π-conjugated moiety than the delocalization of electrons characterizing another of the geometries, ii. computer analysis of the predicted ligand-receptor structure which includes determining whether the ligand in the ligand-receptor structure adopts the geometry characterized by less delocalization, iii. if so, including in the scoring a penalty for reduced delocalization of electrons across the π-conjugated moieties, wherein the magnitude of the penalty is an amount reflecting the reduction of electron delocalization between the configuration of the proposed ligand when complexed with the receptor and the delocalization of an uncomplexed, more delocalized, configuration of the proposed ligand, in which step c. i. includes determining whether the ligand includes one or more rotatable bond paths connecting two chemical moieties which are capable of significant π electron delocalization between the groups across the rotatable bond. i. computer analysis of the proposed ligand molecule data to determine whether the ligand includes at least one π-conjugated moiety having multiple possible geometries, one of the geometries being characterized by less delocalization of electrons across the π-conjugated moiety than the delocalization of electrons characterizing another of the geometries, ii. computer analysis of the predicted ligand-receptor structure which includes determining whether the ligand in the ligand-receptor structure adopts the geometry characterized by less delocalization, iii. if so, including in the scoring a penalty for reduced delocalization of electrons across the π-conjugated moieties, wherein the magnitude of the penalty is an amount reflecting the reduction of electron delocalization between the configuration of the proposed ligand when complexed with the receptor and the delocalization of an uncomplexed, more delocalized, configuration of the proposed ligand,