MOLECULAR DOCKING USING SURFACE COMPLEMENTARITY

A method is described to dock a ligand into a binding site in a protei n on the basis of the complementarity of the intermolecular atomic con tacts. Docking is performed by maximization of a complementarity funct ion that is dependent on atomic contact surface area and the chemical properties of the contacting atoms. The generality and simplicity of t he complementarity function ensure that a wide range of chemical struc tures can be handled. The ligand and the protein are treated as rigid bodies, but displacement of a small number of residues lining the liga nd binding site can be taken into account. The method can assist in th e design of improved ligands by indicating what changes in complementa rity may occur as a result of the substitution of an atom in the ligan d. The capabilities of the method are demonstrated by application to 1 4 protein-ligand complexes of known crystal structure. (C) 1996 Wiley- Liss, Inc.