DOCKING FLEXIBLE MOLECULES - A CASE-STUDY OF 3 PROTEINS

A genetic algorithm (GA) conformation search method is used to dock a series of flexible molecules into one of three proteins. The proteins examined are thermolysin (tmn), carboxypeptidase A (cpa), and dihydrofolate reductase (dfr). In the latter two proteins, the crystal ligand was redocked. For thermolysin, we docked eight ligands into a protein conformation derived from a single crystal structure. The bound conformations of the other ligands in tmn are known. In the cpa and dfr cases, and in seven of thee eight tmn ligands, the GA docking method found conformations within 1.6 Angstrom root mean square (rms) of the relaxed crystal conformation. (C) 1995 by John Wiley & Sons, Inc.