Re-Docking Scheme for Generating Near-Native Protein Complexes by Assembling Residue Interaction Fingerprints

Nobuyuki Uchikoga,Yutaka Akiyama,Takatsugu Hirokawa,Masahito Ohue,Yuri Matsuzaki,Eugene A Permyakov

doi:10.1371/journal.pone.0069365

Abstract

Interaction profile method is a useful method for processing rigid-body docking. After the docking process, the resulting set of docking poses could be classified by calculating similarities among them using these interaction profiles to search for near-native poses. However, there are some cases where the near-native poses are not included in this set of docking poses even when the bound-state structures are used. Therefore, we have developed a method for generating near-native docking poses by introducing a re-docking process. We devised a method for calculating the profile of interaction fingerprints by assembling protein complexes after determining certain core-protein complexes. For our analysis, we used 44 bound-state protein complexes selected from the ZDOCK benchmark dataset ver. 2.0, including some protein pairs none of which generated near-native poses in the docking process. Consequently, after the re-docking process we obtained profiles of interaction fingerprints, some of which yielded near-native poses. The re-docking process involved searching for possible docking poses in a restricted area using the profile of interaction fingerprints. If the profile includes interactions identical to those in the native complex, we obtained near-native docking poses. Accordingly, near-native poses were obtained for all bound-state protein complexes examined here. Application of interaction fingerprints to the re-docking process yielded structures with more native interactions, even when a docking pose, obtained following the initial docking process, contained only a small number of native amino acid interactions. Thus, utilization of the profile of interaction fingerprints in the re-docking process yielded more near-native poses.

Highlights

Prediction of protein-protein docking is one of the most important approaches for understanding the protein-protein interaction networks of living cells
A near-native decoy is defined as a decoy with interactions similar to the native ones, evaluated using the Tanimoto Coefficient (TCIFPnative) values of more than 0.4, as detailed in the Material and Methods section
We found 1187 near-native decoys with L_RMSD value,10.0 Å; this number was comparable to the number of near-native decoys (i.e., 1270) with TCIFPnative value $

Summary

Introduction

Prediction of protein-protein docking is one of the most important approaches for understanding the protein-protein interaction networks of living cells. The rigid-body docking method is most useful for the large-scale prediction of protein-protein interaction networks. The rigid-body docking process, which is the first step in searching the structure of a native complex, generates many candidate protein complexes, referred to as decoys [2,3]. A set of these decoys generally includes many structures that are, by far, different from the native structure. These decoy sets were further searched to identify the near-native decoys of the protein complex

Methods

Results

Conclusion