Protein docking using a genetic algorithm

A genetic algorithm (GA) for protein-protein docking is described, in which the proteins are represented by dot surfaces calculated using the Connolly program. The GA is used to move the surface of one protein relative to the other to locate the area of greatest surface complementarity between the t wo. Surface dots are deemed complementary if their normals are opposed, the ir Connolly shape type is complementary, and their hydrogen bonding or hydr ophobic potential is fulfilled. Overlap of the protein interiors is penaliz ed. The GA is tested on 34 large protein-protein complexes where one or bot h proteins has been crystallized separately. Parameters are established for which 30 of the complexes have at least one near-native solution ranked in the top 100, We have also successfully reassembled a 1,400-residue heptame r based on the top-ranking GA solution obtained when docking two bound subu nits, Proteins 2001;44:44-56. (C) 2001 Wiley-Liss, Inc.