Template-based protein–protein docking exploiting pairwise interfacial residue restraints

Xue, Li
Rodrigues, João
Dobbs, Drena
Dobbs, Drena
Honavar, Vasant
Bonvin, Alexandre
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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.

<p>This article is from <em>Briefings in Bioinformatics </em>(2016), doi: <a href="https://doi.org/10.1093/bib/bbw027">10.1093/bib/bbw027</a>. Posted with permission.</p>
template-based modeling, interface restrained docking, CA-CA-guided docking, AIR-guided docking, refinement