Bryan A. Patel
Department of Chemical Engineering, Princeton University, Princeton, New Jersey 08544, USA

Pablo G. Debenedetti
Department of Chemical Engineering, Princeton University, Princeton, New Jersey 08544, USA

Frank H. Stillinger
Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA

Peter J. Rossky
Department of Chemistry and Biochemistry, Institute for Theoretical Chemistry, University of Texas at Austin, Austin, Texas, USA

Biophys. J. 93, 4116-4127 (2007).

Published ahead of print on August 31, 2007 as doi:10.1529/biophysj.107.108530.

Abstract

We investigate the effect of temperature and pressure on polypeptide conformational stability using a twodimensional square lattice model in which water is represented explicitly. The model captures many aspects of water thermodynamics, including the existence of density anomalies, and we consider here the simplest representation of a protein: a hydrophobic homopolymer. We show that an explicit treatment of hydrophobic hydration is sufficient to produce cold, pressure, and thermal denaturation. We investigate the effects of the enthalpic and entropic components of the water-protein interactions on the overall folding phase diagram, and show that even a schematic model such as the one we consider yields reasonable values for the temperature and pressure ranges within which highly compact homopolymer configurations are thermodynamically stable.