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

We have combined graphics processing unit-accelerated all-atom molecular dynamics with parallel tempering to explore the folding properties of small peptides in implicit solvent on the time scale of microseconds. We applied this methodology to the synthetic β-hairpin, trpzip2, and one of its sequence variants, W2W9. Each simulation consisted of over 8 μs of aggregated virtual time. Several measures of folding behavior showed good convergence, allowing comparison with experimental equilibrium properties. Our simulations suggest that the intramolecular interactions of tryptophan side chains are responsible for much of the stability of the native fold. We conclude that the ff99 force field combined with ff96 φ and ψ dihedral energies and an implicit solvent can reproduce plausible folding behavior in both trpzip2 and W2W9.