Bryan Patel, Chemical Engineering, Princeton University, A214 Engineering Quadrangle, Princeton, NJ 08544, Frank H. Stillinger, Chemistry, Princeton University, Princeton, NJ 08544, and Pablo G. Debenedetti, Princeton University, A-217 E-Quad, Princeton, NJ 08544.
Proteins adopt a unique functional conformation dependent entirely on the primary sequence of amino acids. This native structure is stable within a limited span of temperatures, pressures, and solvent conditions, and in globular proteins is stabilized by the formation of a hydrophobic core from which water is largely excluded. Few of the existing theoretical and computational investigations of protein stability treat water explicitly or are concerned with cold- or pressure-induced unfolding of proteins. We present simulations of a water-explicit protein model that exhibits heat-, cold-, and pressure-induced unfolding. We have recently developed a lattice model of a protein in a hydrogen-bonding solvent. The model solvent, while simplified when compared to real water, displays many of water's thermodynamic anomalies, including a temperature of maximum density [1]. Wang-Landau Density of States simulations [2] of this model reproduce key features of experimentally-determined protein stability curves in the pressure-temperature plane. We explore the evolution of protein stability boundaries upon varying chain length and composition of the model protein, and compare our results to experimental observations
[1] S. Sastry, P.G. Debenedetti, F. Sciortino, and H.E. Stanley. Phys. Rev. E, 53: 6144-6154, 1996
[2] F.G. Wang and D.P. Landau. Phys. Rev. E, 64: 056101, 2001.