Mean first passage time analysis reveals rate-limiting steps, parallel pathways and dead ends in a simple model of protein folding

TL;DR

This study uses mean first passage time analysis on a protein folding model to identify key steps, parallel pathways, and dead ends in the folding process, providing insights into the complex energy landscape.

Contribution

It introduces a kinetic mapping approach to analyze protein folding dynamics, revealing multiple pathways and dead ends in a simplified model.

Findings

Identification of well-defined local minima in folding pathways

Revealing secondary parallel pathways in folding process

Detection of dead ends in the folding landscape

Abstract

We have analyzed dynamics on the complex free energy landscape of protein folding in the FOLD-X model, by calculating for each state of the system the mean first passage time to the folded state. The resulting kinetic map of the folding process shows that it proceeds in jumps between well-defined, local free energy minima. Closer analysis of the different local minima allows us to reveal secondary, parallel pathways as well as dead ends.