Effects of side-chain charges on alpha-helix stability in C-peptide of ribonuclease A studied by multicanonical algorithm

We have performed multicanonical Monte Carlo simulations of C-peptide of ri bonuclease A. Three analogues of the peptide with charged and neutral side chains were used to study the role of side-chain charges in the stability o f the observed alpha-helix. Two dielectric functions, distance-dependent an d constant, are considered to study the effects of solvent contributions. T he results are found to be in accord with the implications of CD and NMR ex periments of C-peptide where it was found that this peptide has high alpha- helix content in aqueous solution and that the removal of the side-chain ch arge of Glu-9(-) enhances helix formation. The lowest-energy conformation o btained by our simulations has an alpha-helix from Ala-4 to Gln-ll in compl ete agreement with the corresponding structure deduced from an X-ray crysta llography experiment of ribonuclease A. The salt bridge between the side ch ains of Glu-2(-) and Arg-10(+), which is known to exist from both NMR and X -ray experiments, is formed only when the side chains are properly charged. Its formation is greatly enhanced when the solvation effects are taken int o account.