Fast kinetics and mechanisms in protein folding

This review describes how kinetic experiments using techniques with dramati cally improved time resolution have contributed to understanding mechanisms in protein folding. Optical triggering with nanosecond laser pulses has ma de it possible to study the fastest-folding proteins as well as fundamental processes in folding for the first time. These include formation of alpha- helices, beta-sheets, and contacts between residues distant in sequence, as well as overall collapse of the polypeptide chain. Improvements in the tim e resolution of mixing experiments and the use of dynamic nuclear magnetic resonance methods have also allowed kinetic studies of proteins that fold t oo fast (greater than or similar to 10(3) s(-1)) to be observed by conventi onal methods. Simple statistical mechanical models have been extremely usef ul in interpreting the experimental results. One of the surprises is that m odels originally developed for explaining the fast kinetics of secondary st ructure formation in isolated peptides are also successful in calculating f olding rates of single domain proteins from their native three-dimensional structure.