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

TL;DR

This study uses long-time simulations with a novel integrator and parallel tempering to evaluate the accuracy of force fields in modeling peptide folding, specifically for the tryptophan zipper peptide, achieving results consistent with experimental data.

Contribution

It introduces a combined simulation approach with a custom integrator and parallel tempering to assess force field accuracy in peptide folding over microsecond timescales.

Findings

Electrostatic interactions of tryptophan sidechains are key to native fold stability.

The ff99 force field with ff96 dihedral energies reproduces plausible folding behavior.

Simulations show convergence with experimental equilibrium properties.

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.