Evaluation of CONSRANK-Like Scoring Functions for Rescoring Ensembles of Protein-Protein Docking Poses

Abstract

Scoring is a challenging step in protein-protein docking, where typically thousands of solutions are generated. In this study, we ought to investigate the contribution of consensus-rescoring, as introduced by Oliva et al. (2013) with the CONSRANK method, where the set of solutions is used to build statistics in order to identify recurrent solutions. We explore several ways to perform consensus-based rescoring on the ZDOCK decoy set for Benchmark 4. We show that the information of the interface size is critical for successful rescoring in this context, but that consensus rescoring in itself performs less well than traditional physics-based evaluation. The results of physics-based and consensus-based rescoring are partially overlapping, supporting the use of a combination of these approaches.

Keywords: docking; interface; prediction; protein–protein interaction; scoring.

FIGURE 1

Number of successes after rescoring the first 2,000 solutions of ZDOCK. The size of the frequency set refers to the set of poses used to compute the residue and contact scores from Eqs 1 and 4. The horizontal red dashed line indicates the number of successes achieved by the ZDOCK native scoring function.

FIGURE 2

Venn diagrams showing the overlap between successful cases with the ZDOCK native scoring function and each of the rescoring functions, when using structural clustering.

FIGURE 3

Number of successes after combination of clusters with the ZDOCK native scoring function. Each panel corresponds to different frequency sets, i.e., sets of poses used to compute the residue and contact scores from Eqs 1 and 4. In any cases, the first 2,000 solutions of ZDOCK are rescored. Gray lines represent data from other panels for comparison.

FIGURE 4

Examples of successful combination of ZDOCK clusters and consensus-based clusters. For each protein–protein complex, the receptor protein is represented as a gray surface and the ligand as a red ribbon. Left column: representative poses of the first five clusters generated with ZDOCK native scoring function, middle column: representative poses of the first five clusters generated with the CONSRANK_U rescoring function, right column: superimposition between near-native docking hit and native structure. For each representative pose, initial ZDOCK rank is indicated next to the color legend. Near-native poses are underlined. 1AVX (Song and Suh, 1998): complex between the porcine trypsin (gray) and soybean inhibitor (red), 1EAW (Friedrich et al., 2002): complex between the catalytic domain of serine proteinase MT-SP1 (gray) and bovine inhibitor (red), 1XQS (Shomura et al., 2005): complex between the human Hsp70 binding protein 1 (gray) and Hsp70 (red), 1E6E (Müller et al., 2001): complex between NADPH:adrenodoxin oxidoreductase (gray) and adrenoxin (red).