Evaluating force field accuracy with long-time simulations of a tryptophan zipper peptide

Abstract

We have combined a custom implementation of the fast multiple-time-stepping LN integrator with parallel tempering to explore folding properties of small peptides in implicit solvent on the time scale of microseconds. We applied this algorithm to the synthetic {\beta}-hairpin trpzip2 and one of its sequence variants W2W9. Each simulation consisted of over 12 {\mu}s of aggregated virtual time. Several measures of folding behavior showed convergence, allowing comparison with experimental equilibrium properties. Our simulations suggest that the electrostatic interaction of tryptophan sidechains is responsible for much of the stability of the native fold. We conclude that the ff99 force field combined with ff96 {\phi} and {\psi} dihedral energies and implicit solvent can reproduce plausible folding behavior in both trpzip2 and W2W9.