Characterization of Protein Folding by Dominant Reaction Pathways

TL;DR

This paper evaluates the Dominant Reaction Pathways (DRP) method for protein folding, demonstrating its accuracy and efficiency in modeling the folding process of a beta-hairpin compared to traditional Molecular Dynamics simulations.

Contribution

It validates the DRP approach against MD simulations for a protein folding model, highlighting its ability to bypass computational challenges and accurately predict folding pathways.

Findings

DRP predictions agree quantitatively with MD results.

Folding initiated by hydrophobic cluster collapse.

DRP efficiently models folding without time-scale decoupling.

Abstract

We assess the reliability of the recently developed approach denominated Dominant Reaction Pathways (DRP) by studying the folding of a 16-residue beta-hairpin, within a coarse-grained Go-type model. We show that the DRP predictions are in quantitative agreement with the results of Molecular Dynamics simulations, performed in the same model. On the other hand, in the DRP approach, the computational difficulties associated to the decoupling of time scales are rigorously bypassed. The analysis of the important transition pathways supports a picture of the beta-hairpin folding in which the reaction is initiated by the collapse of the hydrophobic cluster.