Chiral structure fluctuations predicted by a coarse-grained model of peptide aggregation

Abstract

This work reports on the chiral structure fluctuations of peptide clusters at the early stages of aggregation in a coarse-grained peptide model. Our model reproduces a variety of aggregate structures, from disordered to crystal-like, that are observed experimentally. Unexpectedly, our molecular dynamics simulations showed that the small peptide cluster undergoes chiral structure fluctuations although the underlying implicit solvent model does not assume the chirality of peptides. The chiral fluctuations are quantified through a cluster twist parameter. A simple model is presented where the twist parameter undergoes a stochastic diffusion on a 1D potential surface. The shape of the potential surface changes with the cluster size. The model shows semi-quantitative agreement with the simulations. We hypothesize that the chiral fluctuations at the early stages of peptide aggregation can contribute to the selection of the final fibril structures.