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 just close to the equilibr ium point. Here the 'two-state' transition proceeds without any accumulatio n of metastable intermediates, and only the transition state ('folding nucl eus') is outlined by its key influence on the folding-unfolding kinetics. O ur aim is to review recent experimental and theoretical studies of the fold ing nuclei. (C) 2001 Federation of European Biochemical Societies. Publishe d by Elsevier Science B.V. All rights reserved.