Protein structure modelling and evaluation based on a 4-distance description of side-chain interactions.
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 A for all residues and 0.73 A 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/ 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.
Potapov
Vladimir
V
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Cohen
Mati
M
Inbar
Yuval
Y
Schreiber
Gideon
G
D053179:Caspase 7 / Q000737:chemistry; D053181:Caspase 8 / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D040681:Structural Homology, Protein
D011506:Proteins; D053179:Caspase 7; D053181:Caspase 8