An analysis of side chain interactions and pair correlations within antiparallel beta-sheets: the differences between backbone hydrogen-bonded and non-hydrogen-bonded residue pairs.

Cross-strand pair correlations are calculated for residue pairs in anti-parallel beta-sheet for two cases: pairs whose backbone atoms are hydrogen bonded together (H-bonded site) and pairs which are not (non-H-bonded site). The statistics show that this distinction is important. When glycine is located on the edge of a sheet, it shows a 3:1 preference for the H-bonded site. The strongest observed correlations are for pairs of disulfide-bonded cystines, many of which adopt a close-packed conformation with each cystine in a spiral conformation of opposite chirality to its partner. It is likely that these pairs are a signature for the family of small, cystine-rich proteins. Most other strong positive and negative correlations involve charged and polar residues. It appears that electrostatic compatibility is the strongest factor affecting pair correlation. Significant correlations are observed for beta- and gamma-branched residues in the non-H-bonded site. An examination of the structures shows a directionality in side chain packing. There is a correlation between (1) the directionality in the packing interactions of non-H-bonded beta- and gamma-branched residue pairs, (2) the handedness of the observed enantiomers of chiral beta-branched side chains, and (3) the handedness of the twist of beta-sheet. These findings have implications for the formation of beta-sheets during protein folding and the mechanism by which the sheet becomes twisted.