A simple theory of protein folding kinetics

TL;DR

This paper introduces a simple theoretical model of protein folding kinetics that explains how non-native contacts influence folding mechanisms, aligning with recent simulation observations and highlighting the native state's role as a kinetic hub.

Contribution

The model provides a straightforward framework to understand protein folding dynamics and the impact of non-native interactions, bridging detailed simulations and simpler models.

Findings

Non-native contacts significantly influence folding mechanisms.

The native state acts as a kinetic hub in the folding process.

Changing non-native interaction strength alters the folding pathway.

Abstract

We present a simple model of protein folding dynamics that captures key qualitative elements recently seen in all-atom simulations. The goals of this theory are to serve as a simple formalism for gaining deeper insight into the physical properties seen in detailed simulations as well as to serve as a model to easily compare why these simulations suggest a different kinetic mechanism than previous simple models. Specifically, we find that non-native contacts play a key role in determining the mechanism, which can shift dramatically as the energetic strength of non-native interactions is changed. For protein-like non-native interactions, our model finds that the native state is a kinetic hub, connecting the strength of relevant interactions directly to the nature of folding kinetics.