Hydrogen bond strength and beta-sheet propensities: the role of a side chain blocking effect

Abstract

Amino acid side chains can enhance peptide group hydrogen bond strength in protein structures by obstructing the competing hydrogen bond to solvent in the unfolded state. Available data indicate that the steric blocking effect contributes an average of 0.5 kJ per residue to protein hydrogen bond strength and accounts for the intrinsic beta-sheet propensities of the amino acids. In available data for helical models, the contribution to alpha-helix propensities is obscured especially by large context-dependent effects. These issues are all related by a common side chain-dependent steric clash which disfavors peptide to water H-bond formation, peptide to catalyst complexation in hydrogen exchange reactions (Bai et al., Proteins 17:75-86, 1993), and peptide to peptide H-bonding in the helical main chain conformation (Creamer and Rose, Proc. Natl. Acad. Sci. U.S.A. 89:5937-5941, 1992) but not in beta-strands.