Folding rates and low-entropy-loss routes of two-state proteins.
We develop a simple model for computing the rates and routes of folding of two-state proteins from the contact maps of their native structures. The model is based on the graph-theoretical concept of effective contact order (ECO). The model predicts that proteins fold by "zipping up" in a sequence of small-loop-closure events, depending on the native chain fold. Using a simple equation, with a few physical rate parameters, we obtain a good correlation with the folding rates of 24 two-state folding proteins. The model rationalizes data from Phi-value analysis that have been interpreted in terms of delocalized or polarized transition states. This model indicates how much of protein folding may take place in parallel, not along a single reaction coordinate or with a single transition state.
Weikl
Thomas R
TR
Department of Pharmaceutical Chemistry, University of California, Box 2240, San Francisco, CA 94143-2240, USA. thomas.weikl@mpikg-golm.mpg.de
Dill
Ken A
KA
D000818:Animals; D019277:Entropy; D004795:Enzyme Stability; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013329:Structure-Activity Relationship
D011506:Proteins