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 alpha-helices, turns, and beta-sheets at slow rate-limiting step. The folding rate of such proteins anticorrelate with the length of these beta-secondary structures. It is also assumed that in two-state folding, rapidly folded alpha-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 beta-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 alpha-structure in early intermediates.
Huang
Ji-Tao
JT
The State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China. chengjp@nankai.edu.cn
Cheng
Jin-Pei
JP
Chen
Hui
H
D007700:Kinetics; D008956:Models, Chemical; D017510:Protein Folding; D017433:Protein Structure, Secondary