Template-based protein–protein docking exploiting pairwise interfacial residue restraints. (24th March 2016)

• Record Type: Journal Article
• Authors: Xue, Li C; Rodrigues, João P G L M; Dobbs, Drena; Honavar, Vasant; Bonvin, Alexandre M J J
• Is Part Of: Briefings in bioinformatics. Volume 18:Number 3(2017:May)
• Page Start: 458
• Page End: 466
• Publication Date: 2016-03-24
• Subjects: template-based modeling -- interface restrained docking -- CA-CA-guided docking -- AIR-guided docking -- refinement; Genetics -- Data processing -- Periodicals; Molecular biology -- Data processing -- Periodicals; Genomes -- Data processing -- Periodicals; 572.80285
• DOI: 10.1093/bib/bbw027
• Languages: English
• ISSNs: 1467-5463

Abstract

Abstract: Although many advanced and sophisticated ab initio approaches for modeling protein–protein complexes have been proposed in past decades, template-based modeling (TBM) remains the most accurate and widely used approach, given a reliable template is available. However, there are many different ways to exploit template information in the modeling process. Here, we systematically evaluate and benchmark a TBM method that uses conserved interfacial residue pairs as docking distance restraints [referred to as alpha carbon–alpha carbon (CA-CA)-guided docking]. We compare it with two other template-based protein–protein modeling approaches, including a conserved non-pairwise interfacial residue restrained docking approach [referred to as the ambiguous interaction restraint (AIR)-guided docking] and a simple superposition-based modeling approach. Our results show that, for most cases, the CA-CA-guided docking method outperforms both superposition with refinement and the AIR-guided docking method. We emphasize the superiority of the CA-CA-guided docking on cases with medium to large conformational changes, and interactions mediated through loops, tails or disordered regions. Our results also underscore the importance of a proper refinement of superimposition models to reduce steric clashes. In summary, we provide a benchmarked TBM protocol that uses conserved pairwise interface distance as restraints in generating realistic 3D protein–protein interaction models, when reliable templates are available. The described CA-CA-guided docking protocol is based on the HADDOCK platform, which allows users to incorporate additional prior knowledge of the target system to further improve the quality of the resulting models.