Theoretical study of a landscape of protein folding-unfolding pathways. Folding rates at midtransition

This paper presents a new method for calculating the folding-unfolding rate s of globular proteins. The method is based on solution of kinetic equation s for a network of folding-unfolding pathways of the proteins. The rates ar e calculated in the point of thermodynamic equilibrium between the native a nd completely unfolded states. The method has been applied to all the prote ins listed by Jackson [Jackson, S. E. (1998) Folding Des. 3, R81-R91] and s ome peptides. Although the studied protein chains differ by more than 1 ord er of magnitude in size and exhibit two- as well as three-state kinetics in water, and their folding rates cover more than 11 orders of magnitude, the theoretical estimates are reasonable close to the experimentally measured folding rates in midtransition (the correlation coefficient being as high a s 0.78). This means that the presented theory (having no adjustable paramet ers at all) is consistent with the experimental observations.