Structural bioinformatics Protein–protein interaction specificity is captured by contact preferences and interface composition

Motivation: Large-scale computational docking will be increasingly used in future years to discriminate protein–protein interactions at the residue resolution. Complete cross-docking experiments make in silico reconstruction of protein–protein interaction networks a feasible goal. They ask for efficient and accurate screening of the millions structural conformations issued by the calculations. Results: We propose CIPS (Combined Interface Propensity for decoy Scoring), a new pair potential combining interface composition with residue–residue contact preference. CIPS outperforms several other methods on screening docking solutions obtained either with all-atom or with coarsegrain rigid docking. Further testing on 28 CAPRI targets corroborates CIPS predictive power over existing methods. By combining CIPS with atomic potentials, discrimination of correct conformations in all-atom structures reaches optimal accuracy. The drastic reduction of candidate solutions produced by thousands of proteins docked against each other makes large-scale docking accessible to analysis. Availability and implementation: CIPS source code is freely available at http://www.lcqb.upmc.fr/ CIPS. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.