Protein-DNA docking with a coarse-grained force field

BMC Bioinformatics

Methodology Article

Ranjit Prasad Bahadur¹  Martin Zacharias²  Piotr Setny² 

[1] Indian Institute of Technology Kharagpur, 721302, Kharagpur, India;Physics Department T38, Technical University Munich, James Franck Str. 1, 85748, Garching, Germany;

关键词: Force Field;    Protein Data Bank;    Root Mean Square Deviation;    Shape Complementarity;    Average Root Mean Square Deviation;   

DOI  :  10.1186/1471-2105-13-228

 received in 2012-04-10, accepted in 2012-07-19,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundProtein-DNA interactions are important for many cellular processes, however structural knowledge for a large fraction of known and putative complexes is still lacking. Computational docking methods aim at the prediction of complex architecture given detailed structures of its constituents. They are becoming an increasingly important tool in the field of macromolecular assemblies, complementing particularly demanding protein-nucleic acids X ray crystallography and providing means for the refinement and integration of low resolution data coming from rapidly advancing methods such as cryoelectron microscopy.ResultsWe present a new coarse-grained force field suitable for protein-DNA docking. The force field is an extension of previously developed parameter sets for protein-RNA and protein-protein interactions. The docking is based on potential energy minimization in translational and orientational degrees of freedom of the binding partners. It allows for fast and efficient systematic search for native-like complex geometry without any prior knowledge regarding binding site location.ConclusionsWe find that the force field gives very good results for bound docking. The quality of predictions in the case of unbound docking varies, depending on the level of structural deviation from bound geometries. We analyze the role of specific protein-DNA interactions on force field performance, both with respect to complex structure prediction, and the reproduction of experimental binding affinities. We find that such direct, specific interactions only partially contribute to protein-DNA recognition, indicating an important role of shape complementarity and sequence-dependent DNA internal energy, in line with the concept of indirect protein-DNA readout mechanism.

【 授权许可】

CC BY   
© Setny et al.; licensee BioMed Central Ltd. 2012