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Prediction of side‐chain conformations on protein surfaces
Author(s) -
Xiang Zhexin,
Steinbach Peter J.,
Jacobson Matthew P.,
Friesner Richard A.,
Honig Barry
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21099
Subject(s) - side chain , dihedral angle , conformational isomerism , polar , hydrogen bond , crystallography , surface (topology) , chemistry , surface energy , conformational entropy , diffraction , crystal structure prediction , chain (unit) , materials science , protein structure , umbrella sampling , chemical physics , crystal structure , computational chemistry , molecule , molecular dynamics , mathematics , physics , optics , organic chemistry , geometry , biochemistry , astronomy , polymer
An approach is described that improves the prediction of the conformations of surface side chains in crystal structures, given the main‐chain conformation of a protein. A key element of the methodology involves the use of the colony energy. This phenomenological term favors conformations found in frequently sampled regions, thereby approximating entropic effects and serving to smooth the potential energy surface. Use of the colony energy significantly improves prediction accuracy for surface side chains with little additional computational cost. Prediction accuracy was quantified as the percentage of side‐chain dihedral angles predicted to be within 40° of the angles measured by X‐ray diffraction. Use of the colony energy in predictions for single side chains improved the prediction accuracy for χ 1 and χ 1+2 from 65 and 40% to 74 and 59%, respectively. Several other factors that affect prediction of surface side‐chain conformations were also analyzed, including the extent of conformational sampling, details of the rotamer library employed, and accounting for the crystallographic environment. The prediction of conformations for polar residues on the surface was generally found to be more difficult than those for hydrophobic residues, except for polar residues participating in hydrogen bonds with other protein groups. For surface residues with hydrogen‐bonded side chains, the prediction accuracy of χ 1 and χ 1+2 was 79 and 63%, respectively. For surface polar residues, in general (all side‐chain prediction), the accuracy of χ 1 and χ 1+2 was only 73 and 56%, respectively. The most accurate results were obtained using the colony energy and an all‐atom description that includes neighboring molecules in the crystal (protein chains and hetero atoms). Here, the accuracy of χ 1 and χ 1+2 predictions for surface side chains was 82 and 73%, respectively. The root mean square deviations obtained for hydrogen‐bonding surface side chains were 1.64 and 1.81 Å, with and without consideration of crystal packing effects, respectively. Proteins 2007. © 2007 Wiley‐Liss, Inc.