Sequential Collapse Model for Protein Folding Pathways

A model of protein folding pathways is presented based on the entropy loss induced by loop closure and the protein−solvent interaction. The model is based on a simple physical picture that depends only on knowledge of the primary sequence to reproduce many experimental results. The sequential collapse model (SCM) predicts the sequence of folding events observed in the proton exchange experiments on the folding pathway of apomyoglobin, cytochrome c, and barnase. The SCM addresses the mechanism of the protein folding process by building a sequential picture of the stabilization free energy of folding and the activation barriers that the protein encounters along a sequential folding pathway towards the free energy minimum that prescribes the native structure. The paper (a) describes the theoretical foundations of the SCM, (b) discusses the intermediate states of the folding pathway in the model, and (c) presents detailed results for several globular proteins.