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

Document Type

Article

Publication Date

3-4-1999

Department

Department of Physics

Abstract

We have performed multicanonical Monte Carlo simulations of C-peptide of ribonuclease 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 of the observed α-helix. Two dielectric functions, distance-dependent and constant, are considered to study the effects of solvent contributions. The results are found to be in accord with the implications of CD and NMR experiments of C-peptide where it was found that this peptide has high α-helix content in aqueous solution and that the removal of the side-chain charge of Glu-9- enhances helix formation. The lowest-energy conformation obtained by our simulations has an α-helix from Ala-4 to Gln-11 in complete agreement with the corresponding structure deduced from an X-ray crystallography experiment of ribonuclease A. The salt bridge between the side chains 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 into account

Publication Title

Journal of Physical Chemistry B

Link to Full Text

Share

COinS