CRITICAL-EVALUATION OF THE RESEARCH DOCKING PROGRAM FOR THE CASP2 CHALLENGE

The binding positions of six small-molecule ligands in their complexes with target proteins were predicted using our Research docking progra m for the GASPS challenge, Research uses a Monte Carlo procedure with pairwise energies and allows for the conformational searching of ligan d torsional space, We were able to predict 2 of the 5 noncovalent comp lexes within 2 Angstrom root-mean-square (RMS) of the experimental str uctures as ranked by interaction energy or by a score calculated using our interaction evaluation program, Outrank, In addition, for 4 of th e 5 noncovalent structures we found a docking within 2 Angstrom RMS of the experimental structure within the top 20 dockings as ranked by en ergy, The main limitation in our approach is in the ability of the ene rgy function and Outrank to discriminate among the lowest energy docki ngs, On the other hand, our success in exploring the multidimensional docking space of position, orientation and conformation is encouraging . (C) 1998 Wiley-Liss, Inc.