In the past years, the folding kinetics of many small single-domain proteins
has been characterized by mutational Phi-value analysis. In this article, a
simple, essentially parameter-free model is introduced which derives folding
routes from native structures by minimizing the entropic loop-closure cost
during folding. The model predicts characteristic folding sequences of
structural elements such as helices and beta-strand pairings. Based on few
simple rules, the kinetic impact of these structural elements is estimated from
the routes and compared to average experimental Phi-values for the helices and
strands of 15 small, well-characterized proteins. The comparison leads on
average to a correlation coefficient of 0.62 for all proteins with polarized
Phi-value distributions, and 0.74 if distributions with negative average
Phi-values are excluded. The diffuse Phi-value distributions of the remaining
proteins are reproduced correctly. The model shows that Phi-value
distributions, averaged over secondary structural elements, can often be traced
back to entropic loop-closure events, but also indicates energetic preferences
in the case of a few proteins governed by parallel folding processes.Comment: 24 pages, 3 figures, 2 tables; to appear in "Proteins: Structure,
Function, and Bioinformatics
