Downhill versus two-state protein folding in a statistical mechanical model

TL;DR

This paper uses a statistical mechanical model to compare downhill and two-state protein folding, revealing qualitative differences and temperature-dependent barrierless behavior in 1BBL.

Contribution

It provides an exact equilibrium solution and semianalytical kinetics for protein folding, highlighting differences between downhill and two-state mechanisms.

Findings

Qualitative differences in equilibrium and kinetics between 1BBL and PIN1.

Barrierless folding in 1BBL occurs only at low temperatures.

The model offers insights into the thermodynamics of protein folding.

Abstract

The authors address the problem of downhill protein folding in the framework of a simple statistical mechanical model, which allows an exact solution for the equilibrium and a semianalytical treatment of the kinetics. Focusing on protein 1BBL, a candidate for downhill folding behavior, and comparing it to the WW domain of protein PIN1, a two-state folder of comparable size, the authors show that there are qualitative differences in both the equilibrium and kinetic properties of the two molecules. However, the barrierless scenario which would be expected if 1BBL were a true downhill folder is observed only at low enough temperature.