Mechanical Unfolding of a Simple Model Protein Goes Beyond the Reach of One-Dimensional Descriptions

TL;DR

This paper investigates the complex mechanical unfolding pathways of a simple model protein, revealing that traditional one-dimensional models oversimplify the process and miss key dynamical features.

Contribution

It introduces a Markov-model and transition path theory approach to analyze protein unfolding, showing the limitations of one-dimensional free-energy landscapes.

Findings

Unfolding involves multiple pathways beyond one-dimensional descriptions.

Traditional free-energy vs. end-to-end distance models can be misleading.

Configurations deemed central in 1D models are not actual intermediate states.

Abstract

We study the mechanical unfolding of a simple model protein. The Langevin dynamics results are analyzed using Markov-model methods which allow to describe completely the configurational space of the system. Using transition path theory we also provide a quantitative description of the unfolding pathways followed by the system. Our study shows a complex dynamical scenario. In particular, we see that the usual one-dimensional picture: free-energy vs end-to-end distance representation, gives a misleading description of the process. Unfolding can occur following different pathways and configurations which seem to play a central role in one-dimensional pictures are not the intermediate states of the unfolding dynamics.