Single-Molecule Fluorescence Experiments Determine Protein Folding Transition Path Times

A Fraction of Folding An energy barrier has to be crossed as a protein transforms between folded and unfolded states. Molecular dynamic simulations have observed sharp transitions, with barrier crossing times of less than a microsecond, a fraction of the total folding time; however, this time range has been inaccessible to single-molecule experiments. Chung et al. (p. 981 ) described single-molecule fluorescence experiments that allowed measurement of the transition-path time for a fast-folding protein and to reduce the upper bound for a slow-folding protein. Although the folding rates differed by a factor of 10,000, the transition-path times differ by less than a factor of 5, pointing to energy landscape theory for the explanation.