Incorporating intermolecular distance into protein-protein docking

In this work, intermolecular distance was integrated into the docking of protein-protein complexes. To develop an efficient docking procedure, 22 enzyme-inhibitor targets and 15 antibody-antigen targets were taken from a benchmark set. A three-step approach was adopted, which included global sampling by FTDOCK, filtering by intermolecular distance and ranking by a composite scoring function. For the enzyme-inhibitor targets, the composite scoring function consists of geometry and energy terms. In the set composed of the similar to100 highest ranked candidates for each target, correct complexes were identified for all of the 22 enzyme-inhibitor targets. This docking strategy also succeeded on the four test targets, of which three are CAPRI targets with the same receptor but different binding modes. Interestingly, all three binding modes were correctly predicted. For the antibody-antigen targets, CDR and physical energy were also used in the filtering process and informatics terms were added to the scoring function. The composite score had successful prediction for 13 of the 15 antibody-antigen targets.