Folding nuclei in proteins

When a protein folds or unfolds, it passes through many half-folded microst ates. Only a few of them can accumulate and be seen experimentally, and thi s happens only when the folding (or unfolding) occurs far from the point of thermodynamic equilibrium between the native and denatured states. The uni versal features of folding, though, are observed in the vicinity of the equ ilibrium point. Here the two-state transition proceeds without any accumula tion of metastable intermediates, and only the transition state (folding nu cleus) is outlined by its key influence on the folding/unfolding kinetics. This review covers recent experimental and theoretical studies of folding n uclei.