Potential of Mean Force of Hydrophobic Association:  Dependence on Solute Size

Abstract

The potentials of mean force (PMFs) were determined for systems involving formation of nonpolar dimers composed of methane, ethane, propane, isobutane, and neopentane, respectively, in water, using the TIP3P water model, and in vacuo. A series of umbrella-sampling molecular dynamics simulations with the AMBER force field was carried out for each pair in either water or in vacuo. The PMFs were calculated by using the weighted histogram analysis method (WHAM). The shape of the PMFs for dimers of all five nonpolar molecules is characteristic of hydrophobic interactions with contact and solvent-separated minima and desolvation maxima. The positions of all these minima and maxima change with the size of the nonpolar molecule, that is, for larger molecules they shift toward larger distances. The PMF of the neopentane dimer is similar to those of other small nonpolar molecules studied in this work, and hence the neopentane dimer is too small to be treated as a nanoscale hydrophobic object. The solvent contribution to the PMF was also computed by subtracting the PMF determined in vacuo from the PMF in explicit solvent. The molecular surface area model correctly describes the solvent contribution to the PMF together with the changes of the height and positions of the desolvation barrier for all dimers investigated. The water molecules in the first solvation sphere of the dimer are more ordered compared to bulk water, with their dipole moments pointing away from the surface of the dimer. The average number of hydrogen bonds per water molecule in this first hydration shell is smaller compared to that in bulk water, which can be explained by coordination of water molecules to the hydrocarbon surface. In the second hydration shell, the average number of hydrogen bonds is greater compared to bulk water, which can be explained by increased ordering of water from the first hydration shell; the net effect is more efficient hydrogen bonding between the water molecules in the first and second hydration shells.

The application of the integral equation theory to study the hydrophobic interaction

“…First, we examined the water structure around hydrophobic particles. It has been shown previously 25,45 that water molecules around hydrophobic solutes are more ordered than bulk water. We therefore examined the description of the hydration shells as given by the solute-water PDFs.…”

Hydrophobicity within the three-dimensional Mercedes-Benz model: Potential of mean force

“…44 An idealization of this ordering is the dodecahedral cage of a crystalline methane hydrate in which the number of water molecules hydrating the solute is 20-see Fig. 1.…”

Simulation optimization of spherical non-polar guest recognition by deep-cavity cavitands

“…Recent experiments of ligand interactions with protein hydrophobic recognition pockets, however, indicate binding can be stabilized by enthalpy 18 and the pocket can be dry, 19 nullifying binding facilitated by water release. While molecular simulation studies of hydrophobic interactions have largely focused on the water-mediated interactions between small, spherical species which conform to entropically controlled association, such as methane, [20][21][22][23] more recent simulations of host-guest interactions driven by hydrophobic interactions have focused on the aqueous binding of idealized convex hydrophobic guests with concave hydrophobic pockets and clefts. 24,25 These simulations find the interaction between a spherical hydrophobe with a concave pocket is more strongly favored by the enthalpy of association.…”