2005/02/15 by Thomas R. Weikl, Weikl, Thomas R.
Biochemistry, Genetics and Molecular Biology · Materials Science · Physics and Astronomy · #Biomolecules (q-bio.BM) #Enzyme Structure and Function #FOS: Biological sciences #FOS: Physical sciences #Protein Structure and Dynamics #RNA and protein synthesis mechanisms #Soft Condensed Matter (cond-mat.soft) #cond-mat.soft #q-bio.BM
paper · pdf · doi:10.48550/arxiv.q-bio/0502016
24 pages, 3 figures, 2 tables; to appear in "Proteins: Structure, Function, and Bioinformatics"
arxiv created 2005/02/15 · openalex publication_date 2005/02/15 · arxiv updated 2009/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.