Ranking Docked Models of Protein-Protein Complexes Using Predicted Partner-Specific Protein-Protein Interfaces: A Preliminary Study

Abstract

Computational protein-protein docking is a valuable tool for determining the conformation of complexes formed by interacting proteins. Selecting near-native conformations from the large number of possible models generated by docking software presents a significant challenge in practice. We introduce a novel method for ranking docked conformations based on the degree of overlap between the interface residues of a docked conformation formed by a pair of proteins with the set of predicted interface residues between them. Our approach relies on a method, called PS-HomPPI, for reliably predicting protein-protein interface residues by taking into account information derived from both interacting proteins. PS-HomPPI infers the residues of a query protein that are likely to interact with a partner protein based on known interface residues of the homo-interologs of the query-partner protein pair, i.e., pairs of interacting proteins that are homologous to the query protein and partner protein. Our results on Docking Benchmark 3.0 show that the quality of the ranking of docked conformations using our method is consistently superior to that produced using ClusPro cluster-size-based and energy-based criteria for 61 out of the 64 docking complexes for which PS-HomPPI produces interface predictions. An implementation of our method for ranking docked models is freely available at: http://einstein.cs.iastate.edu/DockRank/.

Keywords: Protein-protein docking; docking scoring function.

Figure 1

Comparison of ranking schemes. The numbers between parentheses in the bottom table are the ranks of normalized Chi-square values computed for each docking case

Figure 2. The ranking of norm_χ² from PS-HomPPI, Lowest Energy, Center Energy, and ClusPro for 61 docking cases

Figure 3

Pair-wise comparisons of different docking scoring methods using Nemenyi test. Methods that are not significantly different (at significant level α=0.05) are grouped together (via connecting lines). The average “rank” of each method over docking cases is shown in the table (and also on the x-axis of the plot).