Czaplewski Cezary, Liwo Adam, Ripoll Daniel R, Scheraga Harold A
Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853-1301, USA.
J Phys Chem B. 2005 Apr 28;109(16):8108-19. doi: 10.1021/jp040691b.
The structuring of water molecules in the vicinity of nonpolar solutes is responsible for hydrophobic hydration and association thermodynamics in aqueous solutions. Here, we studied the potential of mean force (PMF) for the formation of a dimer and trimers of methane molecules in three specific configurations in explicit water to explain multibody effects in hydrophobic association on a molecular level. We analyzed the packing and orientation of water molecules in the vicinity of the solute to explain the effect of ordering of the water around nonpolar solutes on many-body interactions. Consistent with previous theoretical studies, we observed cooperativity, manifested as a reduction of the height of the desolvation barrier for the trimer in an isosceles triangle geometry, but for linear trimers, we observed only anticooperativity. A simple mechanistic picture of hydrophobic association is drawn. The free energy of hydrophobic association depends primarily on the difference in the number of water molecules in the first solvation shell of a cluster and that in the monomers of a cluster; this can be approximated by the molecular surface area. However, there are unfavorable electrostatic interactions between the water molecules from different parts of the solvation shell of a trimer because of their increased orientation induced by the nonpolar solute. These electrostatic interactions make an anticooperative contribution to the PMF, which is clearly manifested for the linear trimer where the multibody contribution due to changes in the molecular surface area is equal to zero. The information theory model of hydrophobic interactions of Hummer et al. also explains the anticooperativity of hydrophobic association of the linear trimers; however, it predicts anticooperativity with a qualitatively identical distance dependence for nonlinear trimers, which disagrees with the results of simulations.
非极性溶质附近水分子的结构决定了水溶液中的疏水水合作用和缔合热力学。在此，我们研究了在明确的水环境中甲烷分子形成二聚体和三聚体的三种特定构型的平均力势（PMF），以在分子水平上解释疏水缔合中的多体效应。我们分析了溶质附近水分子的堆积和取向，以解释非极性溶质周围水的有序排列对多体相互作用的影响。与先前的理论研究一致，我们观察到了协同性，表现为等腰三角形几何构型中三聚体去溶剂化势垒高度的降低，但对于线性三聚体，我们仅观察到反协同性。我们绘制了疏水缔合的简单机理图。疏水缔合的自由能主要取决于簇的第一溶剂化层中的水分子数量与簇单体中的水分子数量之差；这可以通过分子表面积来近似。然而，由于非极性溶质诱导的水分子取向增加，三聚体溶剂化层不同部分的水分子之间存在不利的静电相互作用。这些静电相互作用对PMF产生反协同贡献，这在分子表面积变化引起的多体贡献等于零的线性三聚体中表现得很明显。Hummer等人的疏水相互作用信息理论模型也解释了线性三聚体疏水缔合的反协同性；然而，它预测非线性三聚体的反协同性具有定性相同的距离依赖性，这与模拟结果不一致。
