Origins of Chevron Rollovers in Non-Two-State Protein Folding Kinetics

TL;DR

This paper investigates the origins of chevron rollovers in non-two-state protein folding, linking nonlinear folding rates to native stability and kinetic trapping in folding intermediates, challenging simple two-state models.

Contribution

It reveals that chevron rollovers result from native stability effects and kinetic trapping, providing insights beyond traditional two-state folding models.

Findings

Chevron rollovers are linked to native stability and kinetic trapping.

Simple two-state models do not reproduce chevron rollover behavior.

Native-centric models partially explain folding slowdown phenomena.

Abstract

Chevron rollovers of some proteins imply that their logarithmic folding rates are nonlinear in native stability. This is predicted by lattice and continuum G\=o models to arise from diminished accessibilities of the ground state from transiently populated compact conformations under strongly native conditions. Despite these models' native-centric interactions, the slowdown is due partly to kinetic trapping caused by some of the folding intermediates' nonnative topologies. Notably, simple two-state folding kinetics of small single-domain proteins are not reproduced by common G\=o-like schemes.