Setny Piotr, Baron Riccardo, McCammon J Andrew
Department of Chemistry and Biochemistry, Center for Theoretical Biological Physics, Howard Hughes Medical Institute, Department of Pharmacology, University of California, San Diego and Physics Department, Technical University Munich, 85748 Garching, Germany.
J Chem Theory Comput. 2010 Sep 14;6(9):2866-2871. doi: 10.1021/ct1003077. Epub 2010 Aug 24.
Hydrophobic association is often recognized as being driven by favorable entropic contributions. Here, using explicit solvent molecular dynamics simulations we investigate binding in a model hydrophobic receptor-ligand system which appears, instead, to be driven by enthalpy and opposed by entropy. We use the temperature dependence of the potential of mean force to analyze the thermodynamic contributions along the association coordinate. Relating such contributions to the ongoing changes in system hydration allows us to demonstrate that the overall binding thermodynamics is determined by the expulsion of disorganized water from the receptor cavity. Our model study sheds light on the solvent-induced driving forces for receptor-ligand association of general, transferable relevance for biological systems with poorly hydrated binding sites.
疏水缔合通常被认为是由有利的熵贡献驱动的。在此，我们使用显式溶剂分子动力学模拟，研究了一个模型疏水受体 - 配体系统中的结合情况，结果发现该系统的结合似乎是由焓驱动且受熵阻碍的。我们利用平均力势的温度依赖性来分析沿缔合坐标的热力学贡献。将这些贡献与系统水化的持续变化联系起来，使我们能够证明，整体结合热力学是由受体腔中无序水的排出所决定的。我们的模型研究揭示了溶剂诱导的受体 - 配体缔合驱动力，这对于具有水化程度低的结合位点的生物系统具有普遍的、可转移的相关性。
