Hydrophobic Interactions

The hydrophobic interaction is entropy-driven and thus intrinsically temperature sensitive. For instance, the solubility of methane in water decreases with increasing temperature at low temperatures (after reaching a minimum at about 350 K, the solubility increases with higher temperature [31]). In liquid water, a single water molecule can form four hydrogen bonds with nearby water molecules. However, around an apolar solute, surrounding waters can not form hydrogen bonds with it. Therefore the orientation of waters near the hydrophobic solute is more ordered and the entropy of the system is reduced. For this reason, apolar solutes tend to be lumped together to minimize the number of waters affected by them. The area of the apolar interface is much larger in the unfolded state (Fig. 4 left), and after hydrophobic association, the entropy is increased on the right hand side of Fig. 4.

Figure 4: The hydrophobic effect. Water molecules around a non-polar solute form a cage-like structure, which reduces the entropy. When two non-polar groups associate with each other, water molecules are liberated from the solvation shell, increasing the entropy.

The enthalpy change in Fig. 4 is negative as the distortion of hydrogen bond network near the folded protein becomes less severe. However, the entropy change associated with the order around the solute still dominates the process. Currently experimental data (e.g. from X-ray crystallography or NMR) are scarce and can not distinguish between various existing models of hydrophobic effect. It is also worth noting that there is little evidence from MD to show the enhancement of water structure at the hydrophobic solute interface [14].