Pathways in Two-State Protein Folding

TL;DR

This paper presents a schematic model of two-state protein folding that reconciles the presence of stable intermediates with rapid folding times, introduces a new dynamical transition temperature, and extends to cold unfolding predictions.

Contribution

It introduces a new dynamical transition temperature in protein folding models and generalizes the framework to cold unfolding, providing insights into folding kinetics and stability.

Findings

Proposes a dynamical transition temperature lower than the thermodynamic one.

Reconciles rapid folding with the absence of intermediates.

Predicts relationships between cold and hot unfolding sharpness.

Abstract

The thermodynamics of proteins indicate that folding/unfolding takes place either through stable intermediates or through a two-state process without intermediates. The rather short folding times of the two-state process indicate that folding is guided. We reconcile these two seemingly contradictory observations quantitatively in a schematic model of protein folding. We propose a new dynamical transition temperature which is lower than the thermodynamic one, in qualitative agreement with in vivo measurement of protein stability using E.coli. Finally we demonstrate that our framework is easily generalized to encompass cold unfolding, and make predictions that relate the sharpness of the cold and hot unfolding transitions.