Protein folding roller coaster, one molecule at a time

摘要

Protein folding is a cooperative phenomenon where at the midtransition temperature of. thermal denaturation only fully folded and fully unfolded species coexist in appreciable amounts, while the concentration of partially folded forms is negligible (1) (see Fig. 1). The implication of this finding from early calorimetric studies for kinetics was immediate and dramatic; it suggested that protein folding is a barrier-crossing process whereby folding proteins spend most of the time fluctuating idly in the unfolded state waiting for a rare fluctuation that rapidly carries it to the top of the barrier with a subseq lent "downhill" run to the native state. (Tig. 1). Such a scenario was indeed discovered in folding simulations of simplified, yet nontrivial, sequence-based models in the 1990s (2). The trajectories carrying the protein over the barrier are called transition paths. It is the transition-path trajectories where all folding action occurs, and discerning them step by step holds a key to complete understanding of the mysteries of folding dynamics.