Secondary structure length as a determinant of folding rate of proteins with two- and three-state kinetics.

We present a simple method for determining the folding rates of two- and three-state proteins from the number of residues in their secondary structures (secondary structure length). The method is based on the hypothesis that two- and three-state foldings share a common pattern. Three-state proteins first condense into metastable intermediates, subsequent forming of α-helices, turns, and β-sheets at slow rate-limiting step. The folding rate of such proteins anticorrelate with the length of these β-secondary structures. It is also assumed that in two-state folding, rapidly folded α-helices and turns may facilitate formation of fleeting unobservable 'intermediates' and thus show two-state behavior. There is an inverse relationship between the folding rate and the length of β-sheets and loops. Our study achieves 94.0 and 88.1% correlations with folding rates determined experimentally for 21 three- and 38 two-state proteins, respectively, suggesting that protein-folding rates are determined by the secondary structure length. The kinetic kinds are selected on the basis of a competitive formation of hydrophobic collapse and α-structure in early intermediates. Proteins 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]