How to Use Not-Always-Reliable Binding Site Information in Protein-Protein Docking Prediction

Lin Li,Yi Xiao,Yanzhao Huang,Ivano Eberini

doi:10.1371/journal.pone.0075936

Lin Li, Yi Xiao + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0075936

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Abstract

In many protein-protein docking algorithms, binding site information is used to help predicting the protein complex structures. Using correct and accurate binding site information can increase protein-protein docking success rate significantly. On the other hand, using wrong binding sites information should lead to a failed prediction, or, at least decrease the success rate. Recently, various successful theoretical methods have been proposed to predict the binding sites of proteins. However, the predicted binding site information is not always reliable, sometimes wrong binding site information could be given. Hence there is a high risk to use the predicted binding site information in current docking algorithms. In this paper, a softly restricting method (SRM) is developed to solve this problem. By utilizing predicted binding site information in a proper way, the SRM algorithm is sensitive to the correct binding site information but insensitive to wrong information, which decreases the risk of using predicted binding site information. This SRM is tested on benchmark 3.0 using purely predicted binding site information. The result shows that when the predicted information is correct, SRM increases the success rate significantly; however, even if the predicted information is completely wrong, SRM only decreases success rate slightly, which indicates that the SRM is suitable for utilizing predicted binding site information.

Highlights

Most proteins interact with other proteins or molecules to perform their biological functions
Results on antibody-antigen and dockground 3.0 complexes indicate that softly restricting method (SRM) is much more sensitive to correct information than wrong information
Results on enzyme-inhibitor and other complexes show that using predicted information overall hit count number increases significantly and success rate is raised

Summary

Introduction

Most proteins interact with other proteins or molecules to perform their biological functions. Some algorithms are based on Fast Fourier Transform (FFT) methods [2], such as MolFit [3], 3D-Dock [4,5,6], GRAMM [7], ZDock [8,9], DOT [10], BiGGER [11], HEX [12] and so on. Many of them are combined with other methods to further refine or re-rank the structures obtained in the initial stage [4,13,14] Besides these FFT-based algorithms, some other algorithms are developed, which are able to consider flexibility of proteins during docking procedure, such as RosettaDock [15], ICM-DISC [16], AutoDock [17], and HADDOCK [18]

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