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Open Access Highly Accessed Open Badges 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



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.


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 webcite was developed to enable the use of Hunter and for visualization and interactive exploration of 4-distance distributions.


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.