Simulating the minimum core for hydrophobic collapse in globular proteins

Protein Science : a Publication of the Protein Society
J TsaiM Levitt

Abstract

To investigate the nature of hydrophobic collapse considered to be the driving force in protein folding, we have simulated aqueous solutions of two model hydrophobic solutes, methane and isobutylene. Using a novel methodology for determining contacts, we can precisely follow hydrophobic aggregation as it proceeds through three stages: dispersed, transition, and collapsed. Theoretical modeling of the cluster formation observed by simulation indicates that this aggregation is cooperative and that the simulations favor the formation of a single cluster midway through the transition stage. This defines a minimum solute hydrophobic core volume. We compare this with protein hydrophobic core volumes determined from solved crystal structures. Our analysis shows that the solute core volume roughly estimates the minimum core size required for independent hydrophobic stabilization of a protein and defines a limiting concentration of nonpolar residues that can cause hydrophobic collapse. These results suggest that the physical forces driving aggregation of hydrophobic molecules in water is indeed responsible for protein folding.

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Citations

Dec 19, 2002·Journal of Molecular Biology·Ignacio E Sánchez, Thomas Kiefhaber
May 17, 2001·Proceedings of the National Academy of Sciences of the United States of America·T M RaschkeM Levitt
Jul 13, 2000·Protein Science : a Publication of the Protein Society·C CzaplewskiH A Scheraga
Jan 25, 2008·Proteins·Lada Bendová-BiedermannováJirí Vondrásek
Aug 22, 2013·Protein Science : a Publication of the Protein Society·Kavestri YegambaramRichard L Kingston
Jul 21, 2004·The Journal of Chemical Physics·Qiang HuangCheng-Lung Chen
Jan 12, 2007·Proceedings of the National Academy of Sciences of the United States of America·Manoj V AthawaleShekhar Garde
Dec 2, 1998·Journal of Biomolecular Structure & Dynamics·H A Scheraga
Feb 9, 2005·Physical Review Letters·Mai Suan LiD Thirumalai
Mar 20, 2008·Journal of Chemical Information and Modeling·Edward J BertacciniJames R Trudell
Aug 24, 2007·The Journal of Physical Chemistry. B·Emil SobolewskiHarold A Scheraga
Mar 10, 2001·Journal of Molecular Biology·A Bachmann, T Kiefhaber

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