The structures of the many proteins that have been determined by X-ray diffraction and nuclear magnetic resonance reveal that, in general, the polar and charged amino acids tend to be found on the surface and the aliphatic amino acids tend to be found in the interior. Hydrophobic forces make aliphatic amino acids try to escape from a water environment and to cluster together in the center of a protein away from water.

The precise definition of hydrophobic force and methods of its measurement are currently under rapid development. One way of considering the phenomenon begins by considering the energy and entropy change in moving a neutral, nonpolar amino acid out of the interior of a protein and into the surrounding water (Fig. 1). The entry of a hydrocarbon into water facilitates the formation of structured cages of water molecules around the hydrocarbon molecule. These surround the hydrocarbon but do not significantly interact with it. The energy of formation of these structures actually favors their generation, but the translational and rotational entropy loss required to form the structured water cages inhibits their production. From considerations at this level, we cannot deduce the magnitude of the effects. Those are determined by measuring the relative solubility of different hydrocarbons in water and organic solvents at various temperatures. The results show that the state of the system in which these cages are absent, that is, with the nonpolar amino acids in the interior of the protein, is more probable than the state in which they are present on the protein’s surface.

Fig1. The creation of a water cage around a hydrocarbon in water, when it moves from membrane into water.

Hydrophobic forces can be expected to be strongest at some intermediate temperature between freezing and boiling. Near freezing temperatures, the water throughout the solution becomes more structured, and thus there is little difference between the status of a water molecule in solution or a water molecule in a cage around a hydrophobic group. Alternatively, at high temperatures, little of the water around a hydro phobic group can be be structured. It is melted out of structure. The difference between water around a hydrophobic group and water elsewhere in the solution is maximized at some intermediate temperature. As this difference is important to protein structure, some proteins possess maximum stability at intermediate temperatures. A few are actually denatured upon cooling. A more common manifestation of the hydrophobic forces is the fact that some polymeric structures are destabilized by cooling and depolymerize because the hydrophobic forces holding them together are weaker at lower temperatures.