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A consistent set of statistical potentials for quantifying local side‐chain and backbone interactions
Author(s) -
Fang Qiaojun,
Shortle David
Publication year - 2005
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.20482
Subject(s) - side chain , chemistry , peptide , residue (chemistry) , amide , interaction energy , crystallography , stereochemistry , computational chemistry , molecule , organic chemistry , polymer , biochemistry
The frequencies of occurrence of atom arrangements in high‐resolution protein structures provide some of the most accurate quantitative measures of interaction energies in proteins. In this report we extend our development of a consistent set of statistical potentials for quantifying local interactions between side‐chains and the polypeptide backbone, as well as nearby side‐chains. Starting with ϕ/ψ/χ1 propensities that select for optimal interactions of the 20 amino acid side‐chains with the 2 flanking peptide bonds, the following 3 new terms are added: (1) a distance‐dependent interaction between the side‐chain at i and the carbonyl oxygens and amide protons of the peptide units at i ± 2, i ± 3, and i ± 4; (2) a distance‐dependent interaction between the side‐chain at position i and side‐chains at positions i + 1 through i + 4; and (3) an orientation‐dependent interaction between the side‐chain at position i and side‐chains at i + 1 through i + 4. The relative strengths of these 4 pseudo free energy terms are estimated by the average information content of each scoring matrix and by assessing their performance in a simple fragment threading test. They vary from −0.4–−0.5 kcal/mole per residue for ϕ/ψ/χ1 propensities to a range of −0.15–−0.6 kcal/mole per residue for each of the other 3 terms. The combined energy function, containing no interactions between atoms more than 4 residues apart, identifies the correct structural fragment for randomly selected 15 mers over 40% of the time, after searching through 232,000 alternative conformations. For 14 out of 20 sets of all‐atom Rosetta decoys analyzed, the native structure has a combined score lower than any of the 1700–1900 decoy conformations. The ability of this energy function to detect energetically important details of local structure is demonstrated by its power to distinguish high‐resolution crystal structures from NMR solution structures. Proteins 2005. © 2005 Wiley‐Liss, Inc.