Comparison of Full and Interface Structure Alignment in Template-Based Protein Docking

Abstract

Template-based protein docking, based on sequence/structure similarity to co-crystalyzed complexes complements ab initio docking in predicting the structure of protein-protein complexes. When highly homologous templates for the entire target complex are not available, docking by interface or partial structure alignment (PSA) may provide an adequate solution. Earlier studies indicated that PSA docking can also be used to further refine docking models generated by the full structure alignment (FSA) of the target and the template. We present a thorough comparative analysis of FSA and PSA docking methodologies based on the docking predictions for bound and unbound proteins from the Dockground benchmark set 4 (http://dockground.compbio.ku.edu). Using the unbound structures in docking (i.e. accounting for conformational changes upon binding) decreases the docking performance only slightly for both methods, compared to the docking of the bound structures (by ∼0.3% in top 10 predictions). FSA selects better templates for proteins with different function, whereas PSA provides better templates for multi-domain proteins in which only one domain participates in the interaction (e.g., enzyme-inhibitor). Template structures that have matching CATH annotations with the target yield better docking performance (the success rate 65% and 67% in top 100, for FSA and PSA, respectively, as opposed to 44% and 46% without the CATH annotation). Significant improvement in the unbound docking success rate (from ∼30 to 60% in top 10) is observed when the same template is selected by both PSA and FSA. By adding templates identified by sophisticated sequence/evolutionary based methods, we were able to build near-native models for 90% of complexes in our target set.