Elementary steps in protein folding

The mechanism of protein folding is under intense theoretical and experimental investigation. From stopped-flow mixing experiments we have detailed knowledge of processes slower than about 1 ms, but until recently little was known about folding and unfolding reactions on the microsecond to nanosecond time scale. The use of novel techniques allowed to explore the elementary steps in protein folding, such as intrachain diffusion and formation of alpha-helices, beta-hairpins and loop structures. This brief review discusses the time scales of these early elementary events which are crucial for the understanding of how proteins fold.