TERTIARY STRUCTURE PREDICTION OF C-PEPTIDE OF RIBONUCLEASE-A BY MULTICANONICAL ALGORITHM

We have performed multicanonical Monte Carlo simulations of C-peptide of ribonuclease A. It is known by CD and NMR experiments that this pep tide has high alpha-helix content in aqueous solution and that the sid e-chain charges of residues Glu-2(-) and His-12(+) play an important r ole in the stability of the alpha-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 avera ge helicity as a function of residue number and average distance betwe en two side chains as a function of temperature are calculated. The re sults are found to be in accord with the implications of CD and NMR ex periments. The lowest-energy conformation obtained has an alpha-helix from Ala-4 to Gln-11 in complete agreement with the corresponding stru cture 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 Arg10(+), which is known to exist from both NMR and X-ray experim ents, is formed only when the side chains are properly charged. Its fo rmation is greatly enhanced when the distance-dependent dielectric fun ction is used.