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The role of carbon‐donor hydrogen bonds in stabilizing tryptophan conformations
Author(s) -
Petrella Robert J.,
Karplus Martin
Publication year - 2004
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.10577
Subject(s) - conformational isomerism , hydrogen bond , chemistry , side chain , crystallography , protein structure , stereochemistry , residue (chemistry) , low barrier hydrogen bond , molecule , organic chemistry , biochemistry , polymer
Although most side‐chain torsion angles correspond to low‐energy rotameric positions, deviations occur with significant frequency. One striking example arises in Trp residues, which have an important role in stabilizing protein structures because of their size and mixed hydrophobic/hydrophilic character. Ten percent of Trp side‐chains have unexplained conformations with χ 2 near 0° instead of the expected 90°. The current work is a structural and energetic analysis of these conformations. It is shown that many Trp residues with these orientations are stabilized by three‐center carbon‐donor hydrogen bonds of the form CH … X … HC, where X is a polar hydrogen‐bond acceptor in the environment of the side‐chain. The bridging hydrogen bonds occur both within the Trp side‐chain and between the side‐chain and the local protein backbone. Free energy maps of an isolated Trp residue in an explicit water environment show a minimum corresponding to the off‐rotamer peak observed in the crystallographic data. Bridging carbon‐donor hydrogen bonds are also shown to stabilize on‐rotamer Trp conformations, and similar bridging hydrogen bonds also stabilize some off‐rotamer Asp conformations. The present results suggest a previously unrecognized role for three‐center carbon‐donor hydrogen bonds in protein structures and support the view that the off‐rotamer Trp side‐chain orientations are real rather than artifacts of crystallographic refinements. Certain of the off‐rotamer Trp conformations appear to have a functional role. Proteins 2004;54:000–000. © 2004 Wiley‐Liss, Inc.