Pathways in two-state protein folding

Thermodynamic measurements of proteins indicate that the folding to the nat ive state takes place either through stable intermediates or through a two- state process without intermediates. The rather short folding times of prot eins indicate that folding is guided through some sequence of contact bindi ngs. We discuss the possibility of reconciling a two-state folding event wi th a sequential folding process in a schematic model of protein folding. We propose a new dynamical transition temperature that is lower than the temp erature at which proteins in equilibrium unfold. This is in qualitative agr eement with observations of in vivo protein folding activity quantified by chaperone concentration in Escherichia coli. Finally, we discuss our framew ork in connection with the unfolding of proteins at low temperatures.