Email updates

Keep up to date with the latest news and content from BMC Bioinformatics and BioMed Central.

Open Access Highly Accessed Open Badges Research article

Protein-protein binding site identification by enumerating the configurations

Fei Guo12, Shuai Cheng Li2, Lusheng Wang2* and Daming Zhu1

Author Affiliations

1 School of Computer Science and Technology, Shandong University, Shandong, Jinan 250101, China

2 Department of Computer Science, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong

For all author emails, please log on.

BMC Bioinformatics 2012, 13:158  doi:10.1186/1471-2105-13-158

Published: 6 July 2012



The ability to predict protein-protein binding sites has a wide range of applications, including signal transduction studies, de novo drug design, structure identification and comparison of functional sites. The interface in a complex involves two structurally matched protein subunits, and the binding sites can be predicted by identifying structural matches at protein surfaces.


We propose a method which enumerates “all” the configurations (or poses) between two proteins (3D coordinates of the two subunits in a complex) and evaluates each configuration by the interaction between its components using the Atomic Contact Energy function. The enumeration is achieved efficiently by exploring a set of rigid transformations. Our approach incorporates a surface identification technique and a method for avoiding clashes of two subunits when computing rigid transformations. When the optimal transformations according to the Atomic Contact Energy function are identified, the corresponding binding sites are given as predictions. Our results show that this approach consistently performs better than other methods in binding site identification.


Our method achieved a success rate higher than other methods, with the prediction quality improved in terms of both accuracy and coverage. Moreover, our method is being able to predict the configurations of two binding proteins, where most of other methods predict only the binding sites. The software package is available at webcite for non-commercial use.