Physical reasons for secondary structure stability: alpha-helices in short peptides.

It was recently found that some short peptides (including C- and S-peptide fragments of RNase A) can have considerable helicity in solution, which was considered to be surprising. Does the observed helicity require a new explanation, or is it consistent with previous understanding? In this work we show that this helicity is consistent with the physical theory of secondary structure based on an extension of the conventional Zimm-Bragg model. Without any special modifications, this theory explains reasonably well almost all the experimentally observed dependencies of helicity on pH, temperature, and amino acid replacements. We conclude that the observed "general level" of helicity of C- and S-peptides (5-30% at room temperature and 10-50% near 0 degrees C) is "normal" for short peptides consisting mainly of helix-forming and helix-indifferent residues. The helicity is modified by a multitude of weak specific side chain interactions, many of which are taken into account by the present theory; some discrepancies between the theory and experiment can be explained by weak side-chain-side chain interactions that were neglected. A reasonable coincidence of the theory with experiment suggests that it had been used to investigate the role of local interactions in the formation of alpha-helical "embryos" in unfolded protein chains.