Tertiary Structure Prediction of C-Peptide of Ribonuclease A by Multicanonical Algorithm

Abstract

We have performed multicanonical Monte Carlo simulations of C-peptide of ribonuclease A. It is known by CD and NMR experiments that this peptide has high α-helix content in aqueous solution and that the side-chain charges of residues Glu-2- and His-12+ play an important role in the stability of the α-helix. To confirm these experimental implications, we have used two analogues of the peptide with charged and neutral side chains of Glu-2 and His-12. Two dielectric functions, distance-dependent and constant, are considered to study the effects of solvent contributions. All the simulations were started from random initial conformations. Various thermodynamic quantities such as average helicity as a function of residue number and average distance between two side chains as a function of temperature are calculated. The results are found to be in accord with the implications of CD and NMR experiments. The lowest-energy conformation obtained 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. It is shown that 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 distance-dependent dielectric function is used.