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Open Access Highly Accessed Methodology article

Protein structure modelling and evaluation based on a 4-distance description of side-chain interactions

Vladimir Potapov, Mati Cohen, Yuval Inbar and Gideon Schreiber*

Author Affiliations

Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel

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BMC Bioinformatics 2010, 11:374  doi:10.1186/1471-2105-11-374

Published: 12 July 2010

Abstract

Background

Accurate evaluation and modelling of residue-residue interactions within and between proteins is a key aspect of computational structure prediction including homology modelling, protein-protein docking, refinement of low-resolution structures, and computational protein design.

Results

Here we introduce a method for accurate protein structure modelling and evaluation based on a novel 4-distance description of residue-residue interaction geometry. Statistical 4-distance preferences were extracted from high-resolution protein structures and were used as a basis for a knowledge-based potential, called Hunter. We demonstrate that 4-distance description of side chain interactions can be used reliably to discriminate the native structure from a set of decoys. Hunter ranked the native structure as the top one in 217 out of 220 high-resolution decoy sets, in 25 out of 28 "Decoys 'R' Us" decoy sets and in 24 out of 27 high-resolution CASP7/8 decoy sets. The same concept was applied to side chain modelling in protein structures. On a set of very high-resolution protein structures the average RMSD was 1.47 Å for all residues and 0.73 Å for buried residues, which is in the range of attainable accuracy for a model. Finally, we show that Hunter performs as good or better than other top methods in homology modelling based on results from the CASP7 experiment. The supporting web site http://bioinfo.weizmann.ac.il/hunter/ webcite was developed to enable the use of Hunter and for visualization and interactive exploration of 4-distance distributions.

Conclusions

Our results suggest that Hunter can be used as a tool for evaluation and for accurate modelling of residue-residue interactions in protein structures. The same methodology is applicable to other areas involving high-resolution modelling of biomolecules.