Oil and water do not mix. The disaffinity of oil for water, with its unusual temperature dependence, is called the hydrophobic effect. It is important to understand the factors underlying the hydrophobic effect because they appear to play key roles in membrane and micelle formation, protein folding, ligand-protein and proteinprotein binding, chromatographic retention, possibly nucleic acid interactions, and the partitioning of drugs, metabolites, and toxins throughout the environment and living systems. Here, we survey experimental and theoretical studies of nonpolar solute partitioning into water. We note that the hydrophobic effect is not just due to "water ordering" and not merely due to small size effects of water. The properties vary substantially with temperature and solute shape. Also, we discuss the limitations of using oil/water partitioning as the basis for some thermodynamic models in chemistry and biology. † Graduate Group in Biophysics.

In a previous issue [1], we exploited a comic by Carl Barks, "The Big Bin on Killmotor Hill", as a starting point for illustrating the anomaly of water, i.e., that water expands when freezing. We can continue here with Barks' most passionate fan, Keno Don Rosa 1 , examining his "Return to Plain Awful" [1], which is a sequel of Barks' "Lost in the Andes!"[2], conceived as a tribute for the 40 th anniversary of this comics.

Hydrophobic interactions are investigated by molecular dynamics computer simulations of the free energy, entropy, and internal energy of association of two methane molecules in water. Recently we reported a computer simulation calculation of the entropy of association of methane in water [J. Am. Chem. Soc. 114, 5875 (1992)], where entropy drives nonpolar solutes together at short distances. Here this method is compared with two other general methods for the calculation of the entropic contribution to the free energy. The calculated thermodynamic quantities for methane association are in good agreement with available experimental measurements. Solute contact configurations are found to be of greater importance than solvent-separated configurations, in conflict with earlier theoretical and simulation studies of similar systems. In some cases, this conflict may be understood in terms of differences in the assumed, model intermolecular potential energies.