T Dependence on Dielectric Model and pH in a Synthetic Helical Peptide Studied

Monte Carlo simulated annealing is applied to the tertiary structure predic-tion of a 17-residue synthetic peptide, which is known by experiment to exhibit high helical content at low pH. Two dielectric models are considered: sigmoidal distance-dependent dielectric function and a constant dielectric function (c = 2). Starting from completely random initial conformations, our simulations for both dielectric models at low pH gave many helical conformations. The obtained low-energy conformations are compared with the NOESY cross peak data for both main chain and side chains, and it is shown that the results for the sigmoidal d&ectric function agree with the experimental data more than for the constant dielectric function. The failure of the constant dielectric function is interpreted to be due to the insufficiently screened repulsive electrostatic interactions among four positively charged residues at low pH. The results of the sigmoidal dielectric func-tion predict the existence of two disjoint helices around residues 5-9 and 11-16. Simulations with high pH, on the other hand, hardly gave a helical conformation, which is also in accord with the experiment. Our results are compared with the previous molecular dynamics simulations of the same peptide.