Effects of geometry and chemistry on hydrophobic solvation.

Inserting an uncharged van der Waals (vdw) cavity into water disrupts the distribution of water and creates attractive dispersion interactions between the solvent and solute. This free-energy change is the hydrophobic solvation energy (ΔG(vdw)). Frequently, it is assumed to be linear in the solvent-accessible surface area, with a positive surface tension (γ) that is independent of the properties of the molecule. However, we found that γ for a set of alkanes differed from that for four configurations of decaalanine, and γ = -5 was negative for the decaalanines. These findings conflict with the notion that ΔG(vdw) favors smaller A. We broke ΔG(vdw) into the free energy required to exclude water from the vdw cavity (ΔG(rep)) and the free energy of forming the attractive interactions between the solute and solvent (ΔG(att)) and found that γ < 0 for the decaalanines because -γ(att) > γ(rep) and γ(att) < 0. Additionally, γ(att) and γ(rep) for the alkanes differed from those for the decaalanines, implying that none of ΔG(att), ΔG(rep), and ΔG(vdw) can be computed with a constant surface tension. We also showed that ΔG(att) could not be computed from either the initial or final water distributions, implying that this quantity is more difficult to compute than is sometimes assumed. Finally, we showed that each atom's contribution to γ(rep) depended on multibody interactions with its surrounding atoms, implying that these contributions are not additive. These findings call into question some hydrophobic models.