Fig. 4

The folding and denaturation pathways of a protein that is metastable in its native conformation. The fast folding pathway in vivo starts from a high-energy state generated by ribosome/chaperone complex in the process that is described in [67, 68] and in the text. The native structure of this protein occupies a metastable local thermodynamic minimum (A). If the protein escapes this local thermodynamic minimum, it can either move to another local minimum (B, C) from which refolding is possible (reversible denaturation), or it can move into conformations with much lower Gibbs free energy, from which it cannot refold (irreversible denaturation). Multiple red arrows illustrate the multiplicity of the denaturation pathways