期刊
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
卷 78, 期 6, 页码 1503-1519出版社
WILEY
DOI: 10.1002/prot.22668
关键词
flexible docking; backbone flexibility; modeling protein-protein docking; normal modes; prediction of protein-protein interactions
资金
- Israel Science Foundation [1403/09]
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- NIH [P41 RR-01081]
- Tel-Aviv University
- Israel Academy of Sciences and Humanities
- NIH, National Cancer Institute, Center for Cancer Research
Upon binding, proteins undergo conformational changes. These changes often prevent rigid-body docking methods from predicting the 3D structure of a complex from the unbound conformations of its proteins. Handling protein backbone flexibility is a major challenge for docking methodologies, as backbone flexibility adds a huge number of degrees of freedom to the search space, and therefore considerably increases the running time of docking algorithms. Normal mode analysis permits description of protein flexibility as a linear combination of discrete movements (modes). Low-frequency modes usually describe the large-scale conformational changes of the protein. Therefore, many docking methods model backbone flexibility by using only few modes, which have the lowest frequencies. However, studies show that due to molecular interactions, many proteins also undergo local and small-scale conformational changes, which are described by high-frequency normal modes. Here we present a new method, Fiber Dock, for docking refinement which models backbone flexibility by an unlimited number of normal modes. The method iteratively minimizes the structure of the flexible protein along the most relevant modes. The relevance of a mode is calculated according to the correlation between the chemical forces, applied on each atom, and the translation vector of each atom, according to the normal mode. The results show that the method successfully models backbone movements that occur during molecular interactions and considerably improves the accuracy and the ranking of rigid-docking models of protein protein complexes. A web server for the Fiber Dock method is available at: http://bioinfo3d.cs.tau.ac.il/FiberDock.
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