The hydrophobic effect: is water afraid, or just not that interested?

Our understanding of the hydrophobic effect has advanced greatly since 1990, with the help of experimental, theoretical, and computer simulation results. The key hydrophobic signature of positive ∆ C ° P and negative ∆ S ° at room temperature has been interpreted in light of the importance of solvent cavity creation, solvent-excluded volume, and solute–water intermolecular forces, along with some unusual thermodynamic properties of pure water. Application of the hydrophobic effect to the hydration of small nonpolar solutes, protein folding stability, and protein–ligand binding is discussed in detail in this review, with an emphasis on thermodynamic analyses and interpretations.