M. Vijayakumar et al., Hydrogen bonds between short polar side chains and peptide backbone: Prevalence in proteins and effects on helix-forming propensities, PROTEINS, 34(4), 1999, pp. 497-507
A survey of 322 proteins showed that the short polar (SP) side chains of fo
ur residues, Thr, Ser, Asp, and Asn, have a very strong tendency to form hy
drogen 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 stabi
lity by a hydrogen bond with the amide of the N3 or N2 residue is well esta
blished. 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 back
bone carbonyl for the same hydrogen-bonding partner (i.e., the backbone ami
de) and thus SP residues tend to break backbone carbonyl-amide hydrogen bon
ds. The proposition that this is the origin for the low propensities of SP
residues in the middle of ex helices (relative to those of nonpolar residue
s) was tested. The combined effects of restricting side-chain rotamer confo
rmations (documented by Creamer and Rose, Proc Acad Sci USA, 1992;89:5937-5
941; Proteins, 1994;19:85-97) and excluding side- chain to backbone hydroge
n bonds by the helix were quantitatively analyzed. These were found to corr
elate 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 los
s of side-chain conformational entropy needs to be considered). Proteins 19
99;34:497-507. (C) 1999 Wiley-Liss, Inc.