Scoring docked conformations generated by rigid-body protein-protein docking

Rigid-body methods, particularly Fourier correlation techniques, are very e fficient for docking bound (co-crystallized) protein conformations using me asures of surface complementarity as the target function. However, when doc king unbound (separately crystallized) conformations, the method generally yields hundreds of false positive structures with good scores but high root mean square deviations (RMSDs). This paper describes a two-step scoring al gorithm that can discriminate near-native conformations (with less than 5 A ngstrom RMSD) from other structures. The first step includes two rigid-body filters that use the desolvation free energy and the electrostatic energy to select a manageable number of conformations for further processing, but are unable to eliminate all false positives. Complete discrimination is ach ieved in the second step that minimizes the molecular mechanics energy of t he retained structures, and re-ranks them with a combined free-energy funct ion which includes electrostatic, solvation, and van der Waals energy terms , After minimization, the improved fit in near-native complex conformations provides the free-energy gap required for discrimination, The algorithm ha s been developed and tested using docking decoys, i.e., docked conformation s generated by Fourier correlation techniques. The decoy sets are available on the web for testing other discrimination procedures, Proteins 2000;40:5 25-537, (C) 2000 Wiley-Liss, Inc.