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Hydrogen bonds between short polar side chains and peptide backbone: Prevalence in proteins and effects on helix‐forming propensities
Author(s) -
Vijayakumar M.,
Qian Hong,
Zhou HuanXiang
Publication year - 1999
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/(sici)1097-0134(19990301)34:4<497::aid-prot9>3.0.co;2-g
Subject(s) - polar , hydrogen bond , side chain , helix (gastropod) , peptide , chemistry , crystallography , materials science , biophysics , biochemistry , biology , physics , molecule , organic chemistry , astronomy , ecology , snail , polymer
A survey of 322 proteins showed that the short polar (SP) side chains of four residues, Thr, Ser, Asp, and Asn, have a very strong tendency to form hydrogen bonds with neighboring backbone amides. Specifically, 32% of Thr, 29% of Ser, 26% of Asp, and 19% of Asn engage in such hydrogen bonds. When an SP residue caps the N terminal of a helix, the contribution to helix stability by a hydrogen bond with the amide of the N3 or N2 residue is well established. When an SP residue is in the middle of a helix, the side chain is unlikely to form hydrogen bonds with neighboring backbone amides for steric and geometric reasons. In essence the SP side chain competes with the backbone carbonyl for the same hydrogen‐bonding partner (i.e., the backbone amide) and thus SP residues tend to break backbone carbonyl‐amide hydrogen bonds. The proposition that this is the origin for the low propensities of SP residues in the middle of α helices (relative to those of nonpolar residues) was tested. The combined effects of restricting side‐chain rotamer conformations (documented by Creamer and Rose, Proc Acad Sci USA, 1992;89:5937–5941; Proteins, 1994;19:85–97) and excluding side‐ chain to backbone hydrogen bonds by the helix were quantitatively analyzed. These were found to correlate strongly with four experimentally determined scales of helix‐forming propensities. The correlation coefficients ranged from 0.72 to 0.87, which are comparable to those found for nonpolar residues (for which only the loss of side‐chain conformational entropy needs to be considered). Proteins 1999;34:497–507. © 1999 Wiley‐Liss, Inc.