Diffusive dynamics of contact formation in disordered polypeptides

TL;DR

This study uses all-atom simulations to understand contact formation dynamics in disordered polypeptides, validating simplified models and revealing reduced diffusivity at small separations affecting protein folding insights.

Contribution

It demonstrates that 1D diffusion models can accurately capture contact formation times when informed by all-atom simulations, highlighting the importance of configurational space and diffusivity variations.

Findings

Simulation results match experimental quenching times when considering water viscosity.

1D diffusion models are validated against all-atom simulation data.

Reduced diffusivity at small separations significantly influences contact formation rates.

Abstract

Experiments measuring contact formation between a probe and quencher in disordered chains provide information on the fundamental dynamical timescales relevant to protein folding, but their interpretation usually relies on simplified one-dimensional (1D) diffusion models. Here, we use all-atom molecular simulations to capture both the time-scales of contact formation, as well as the scaling with the length of the peptide for tryptophan triplet quenching experiments. Capturing the experimental quenching times depends on the water viscosity, but more importantly on the configurational space explored by the chain. We also show that very similar results are obtained from Szabo-Schulten-Schulten theory applied to a 1D diffusion model derived from the simulations, supporting the validity of such models. However, we also find a significant reduction in diffusivity at small separations, those which are most important in determining the quenching rate.