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Title:Stirred spin glass models of in vivo protein folding
Author(s):Gulukota, Kamalakar
Doctoral Committee Chair(s):Wolynes, P.G.
Department / Program:Biophysics and Computational Biology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Chemistry, Biochemistry
Chemistry, Physical
Biophysics, General
Abstract:The similarity between spin glasses and proteins is that both have complex energy landscapes with multiple energy minima and barriers. The approach to equilibrium in such systems has been previously studied. We present here a "stirred" spin glass whose equilibrium is constantly being perturbed by a possibility for effectively leaving and reentering the system. Our results indicate that such stirring causes a spread in the equilibrium occupancy of energy levels and, probably lower or abolish the freezing temperature of the system.
We used this stirred spin-glass picture to analyze in vivo protein folding. The statistical energy landscape picture of protein folding has led to the understanding that a necessary condition for in vitro foldability is the presence of some sort of guiding forces in the energy landscape leading to folding funnels. Chaperone molecules which are the important actors in in vivo protein folding are known to act basically by repeated binding and unbinding to partially unfolded protein molecules. I describe how this binding and unbinding is equivalent to leaving and re-entering the system and thus to a stirred spin glass. I describe a model of chaperone action based on this repetitive binding, giving rise to a possibility of kinetic proofreading. I also studied models where chaperone binding is locally biased depending upon the similarity to the native state. Our results show that the presence of guiding forces in the energy landscape is necessary for folding within the Levinthal time in vitro. While unbiased binding can help folding modestly, the results show that biased chaperone binding can form the nonequilibrium analog of a folding funnel and dramatically improve yields and shorten timescales.
Issue Date:1994
Rights Information:Copyright 1994 Gulukota, Kamalakar
Date Available in IDEALS:2011-05-07
Identifier in Online Catalog:AAI9512383
OCLC Identifier:(UMI)AAI9512383

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