Protein-protein interaction specificity is captured by contact preferences and interface composition

• Published in: Bioinformatics 2018-02, Vol.34 (3), p.459-468
• Main Authors: Nadalin, Francesca, Carbone, Alessandra
• Format: Article
• Language: English
• Subjects: bioinformatics; Computational Biology - methods; Life Sciences; Molecular Docking Simulation; Original Papers; Protein Interaction Mapping - methods; protein-protein interactions; proteins; screening; Sensitivity and Specificity; Software
• ISSN: 1367-4803; 1460-2059; 1460-2059; 1367-4811
• DOI: 10.1093/bioinformatics/btx584

Abstract 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 coarse-grain 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. Supplementary information Supplementary data are available at Bioinformatics online.