Alpha-helix folding by Monte Carlo simulated annealing in isolated C-peptide of ribonuclease A.

Conformation of the C-peptide fragment of RNase A is calculated by Monte Carlo simulated annealing. We adopt the total potential energy as given by the sum of generic interatomic energies whose parameters are determined separately for each amino acid without referring to the empirical structure of the C-peptide. The simulation is carried out in a completely unrestricted way without imposing any weight towards given final destinations. Starting from completely random initial conformations and minimizing the total potential energy with respect to main-chain dihedral angles and side-chain torsion angles, we have obtained partial alpha-helix structure with a high probability (approximately 40%). The energetically most favourable structure exhibits a 2.5-turn alpha-helix at the location identical with that of the 3-turn alpha-helix in the native enzyme molecule. Classification of conformations obtained in the simulation into clusters of similar structure shows that our simulation indeed predicts the alpha-helix structure for the isolated C-peptide with specific charged residues. The results of simulation with various amino acid substitutions are also found to be consistent with the experimental implication for the importance of intramolecular ionic interactions for alpha-helix stability for this peptide.