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

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.