| Abstract
| - A theoretical approach is developed to quantify hydrophobic hydration and interactions on a molecular scale,with the goal of insight into the molecular origins of hydrophobic effects. The model is based on thefundamental relation between the probability for cavity formation in bulk water resulting from molecular-scale density fluctuations and the hydration free energy of the simplest hydrophobic solutes, hard particles.This probability is estimated using an information theory (IT) approach, incorporating experimentally availableproperties of bulk water: the density and radial distribution function. The IT approach reproduces the simplesthydrophobic effects: hydration of spherical nonpolar solutes, the potential of mean force (PMF) betweenmethane molecules, and solvent contributions to the torsional equilibrium of butane. Applications of thisapproach to study temperature and pressure effects provide new insights into the thermodynamics and kineticsof protein folding. The IT model relates the hydrophobic-entropy convergence observed in protein unfoldingexperiments to the macroscopic isothermal compressibility of water. A novel explanation for pressuredenaturation of proteins follows from an analysis of the pressure stability of hydrophobic aggregates, suggestingthat water penetrates the hydrophobic core of proteins at high pressures. This resolves a long-standing puzzle,whether pressure denaturation contradicts the hydrophobic-core model of protein stability. Finally, issues of“dewetting” of molecularly large nonpolar solutes are discussed in the context of a recently developedperturbation theory approach.
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