Origin of entropy convergence in hydrophobic hydration and protein folding

Abstract

An information theory model is used to construct a molecular explanation why hydrophobic solvation entropies measured in calorimetry of protein unfolding converge at a common temperature. The entropy convergence follows from the weak temperature dependence of occupancy fluctuations for molecular-scale volumes in water. The macroscopic expression of the contrasting entropic behavior between water and common organic solvents is the relative temperature insensitivity of the water isothermal compressibility. The information theory model provides a quantitative description of small molecule hydration and predicts a negative entropy at convergence. Interpretations of entropic contributions to protein folding should account for this result.