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Loop‐closure events during protein folding: Rationalizing the shape of Φ‐value distributions
Author(s) -
Weikl Thomas R.
Publication year - 2005
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20504
Subject(s) - closure (psychology) , loop (graph theory) , folding (dsp implementation) , value (mathematics) , statistical physics , mechanics , mathematics , biological system , physics , biology , statistics , combinatorics , structural engineering , engineering , political science , law
In the past years, the folding kinetics of many small single‐domain proteins has been characterized by mutational Φ‐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 β‐strand pairings. Based on few simple rules, the kinetic impact of these structural elements is estimated from the routes and compared to average experimental Φ‐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 Φ‐value distributions, and 0.74 if distributions with negative average Φ‐values are excluded. The diffuse Φ‐value distributions of the remaining proteins are reproduced correctly. The model shows that Φ‐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. Proteins 2005. © 2005 Wiley‐Liss, Inc.