Pressure Denaturation of Proteins in Water: Revisiting a Heteropolymer Collapse Model

Understanding the environmental factors that cause proteins to unfold from their native conformations to form biologically-inactive or denatured states represents one of the most important challenges in the biological and pharmaceutical sciences. Although it has been known for some time that proteins can be denatured by heating or cooling at high or low pressure, only semiempirical thermodynamic approaches have been developed for predicting the range of protein stability in the pressure-temperature plane [1]. An analytical molecular-level theory that can give insights into the state-dependent driving forces for unfolding would be an extremely useful complement to recent experiments (see, e.g. [2]), information theory approaches [3], and computer simulations [4].