The ICM-DISCO (Docking and Interface Side-Chain Optimization) protein–protein-docking method is a direct stochastic global energy optimization from multiple starting positions of the ligand. The first step is performed by docking of a rigid all-atom ligand molecule to a set of soft receptor potentials precalculated on a 0.5 Å grid from realistic solvent-corrected force-field energies. This step finds the correct solution as the lowest energy conformation in almost 100% of the cases in which interfaces do not change on binding. The second step is needed to deal with the induced changes and includes the global optimization of the interface side-chains of up to 400 best solutions. The CAPRI predictions were performed fully automatically with this method. Available experimental information was included as a filtering step to favor expected docking surfaces. In three of the seven proposed targets, the ICM-DISCO method found a good solution (>50% of correct contacts) within the five submitted models. The procedure is global and fully automated. We demonstrate that the algorithm handles the induced changes of surface side-chains but is less successful if the backbone undergoes large-scale rearrangements. Proteins 2003;52:113–117. © 2003 Wiley-Liss, Inc.