Center for Biophysics & Computational Biology/ICMS, Department of Chemistry , Temple University , Philadelphia , Pennsylvania 19122 , United States.
Department of Science , Borough of Manhattan Community College, The City University of New York , New York , New York 10007 , United States.
J Phys Chem B. 2019 Oct 10;123(40):8378-8386. doi: 10.1021/acs.jpcb.9b07028. Epub 2019 Oct 1.
This study investigates the role of hydration and its relationship to the conformational equilibrium of the host molecule β-cyclodextrin. Molecular dynamics simulations indicate that the unbound β-cyclodextrin exhibits two state behavior in explicit solvent due to the opening and closing of its cavity. In implicit solvent, these transitions are not observed, and there is one dominant conformation of β-cyclodextrin with an open cavity. Based on these observations, we investigate the hypothesis that the expulsion of thermodynamically unfavorable water molecules into the bulk plays an important role in controlling the accessibility of the closed macrostate at room temperature. We compare the results of the molecular mechanics analytical generalized Born plus nonpolar solvation approach to those obtained through grid inhomogeneous solvation theory analysis with explicit solvation to elucidate the thermodynamic forces at play. The work illustrates the use of continuum solvent models to tease out solvation effects related to the inhomogeneity and the molecular nature of water and demonstrates the key role of the thermodynamics of enclosed hydration in driving the conformational equilibrium of molecules in solution.
本研究探讨了水合作用的作用及其与主体分子β-环糊精构象平衡的关系。分子动力学模拟表明，由于空腔的开启和关闭，未结合的β-环糊精在明溶剂中表现出两种状态行为。在隐溶剂中，这些转变没有被观察到，并且β-环糊精只有一种具有开口空腔的主要构象。基于这些观察，我们研究了这样一种假设，即热力学上不利的水分子被逐出到体相在控制室温下封闭宏观状态的可及性方面起着重要作用。我们将分子力学分析的广义 Born 加非极性溶剂化方法的结果与通过显式溶剂化进行网格不均匀溶剂化理论分析获得的结果进行比较，以阐明起作用的热力学力。这项工作说明了使用连续溶剂模型来梳理与不均匀性和水的分子性质有关的溶剂化效应，并展示了封闭水合热力学在驱动溶液中分子构象平衡方面的关键作用。
