One-dimensional potential barrier model of protein folding with intermediates

Abstract

Protein folding is modeled as one-dimensional diffusion in a potential with square wells representing folding species and square barriers representing transitions among the species. Within the context of the model, one or more intermediate species can either speed up or slow down folding, depending on their energy and on the potential barrier(s) to the final folded state. Intermediate species in deep potential wells may reduce the probability in the final state, as well as slowing the overall folding process. The potential barrier model is consistent with protein folding taking place by diffusion, collision and coalescence of marginally stable subunits of the protein in a sequential but, in principle, arbitrary order, as in the diffusion-collision model. Using parameters taken from the structures of three-helix bundle proteins the potential barrier model gives folding rates consistent with recent experiments on these proteins.