J Phys Chem B. 2018 Dec 13;122(49):11695-11701. doi: 10.1021/acs.jpcb.8b07773. Epub 2018 Oct 9.
Water, despite being a driving force in biochemical processes, has an elusively complex microscopic behavior. While water can increase its local density near amphiphilic protein surfaces, water is also thought to evaporate from hydrophobic surfaces and cavities, an effect known as "dewetting". The existence and extent of dewetting effects remains elusive due to the difficulty in observing clear "drying" transitions in experiments or simulations. Here, we use explicit solvent molecular dynamics (MD) simulations to study the molecular solvation at the binding interfaces of two distinctive molecular complexes: the highly hydrophilic barnase-barstar and the highly hydrophobic MDM2-p53. Our simulations, in conjunction with simple volumetric analyses, reveal a strikingly different water behavior at the binding interfaces of these two molecular complexes. In both complexes, we observe significant changes in the water local density as the two proteins approach, supporting the existence of a clear dewetting transition in the case of MDM2-p53, with an onset distance of 5.6-7.6 Å. Furthermore, the solvation analysis reported herein is a valuable tool to capture and quantify persistent or transient dewetting events in future explicit solvent MD simulations.
水虽然是生化过程的驱动力，但它的微观行为却异常复杂。尽管水可以在两亲性蛋白质表面附近增加局部密度，但水也被认为会从疏水性表面和腔中蒸发，这种效应被称为“去湿”。由于在实验或模拟中难以观察到明确的“干燥”转变，因此去湿效应的存在和程度仍然难以捉摸。在这里，我们使用显式溶剂分子动力学（MD）模拟来研究两种不同分子复合物结合界面处的分子溶剂化作用：高度亲水的 barnase-barstar 和高度疏水的 MDM2-p53。我们的模拟结合简单的体积分析，揭示了这两种分子复合物结合界面处水行为的显著差异。在这两种复合物中，我们观察到随着两种蛋白质的接近，水局部密度发生了显著变化，支持 MDM2-p53 中存在明显的去湿转变，起始距离为 5.6-7.6Å。此外，本文报道的溶剂化分析是一种在未来显式溶剂 MD 模拟中捕获和量化持久或瞬态去湿事件的有价值工具。
