Pressure Induced Wetting and Dewetting of the Nonpolar Pocket of Deep-Cavity Cavitands in Water
Pressure Induced Wetting and Dewetting of the Nonpolar Pocket of Deep-Cavity Cavitands in Water
复制标题
水中深腔空穴非极性区的压力诱导润湿和反润湿
DOI：
10.1021/acs.jpcb.0c02568
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Ashbaugh, Henry S.
中科院分区：
文献类型：
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作者：
Tang, Du;Dwyer, Tobias;Bukannan, Hussain;Blackmon, Odella;Delpo, Courtney;Barnett, J. Wesley;Gibb, Bruce C.;Ashbaugh, Henry S.
疏水相互作用驱动非极性配体与水溶液中蛋白质和超分子物质的油性口袋结合。因此，预期主体口袋的润湿在确定客体结合的热力学中起关键作用。在这里，我们使用分子模拟研究的润湿和去湿的非极性口袋的一系列深腔空腔在水中的压力的影响。空腔袋的入口用指向向上或向内的袋的非极性（甲基）和极性（羟基）基团官能化。我们发现润湿的口袋是有利于由羟基和去湿有利于由甲基。口袋中的沃茨的分布被发现表现出两个国家之间的湿态和干态的自由能垒的平衡。此外，我们表明，口袋水合的cavitands可以崩溃到一个统一的吸附等温线，通过假设每个cavitands口袋内的有效压力不同的移位压力，这取决于化学身份和数量的功能团放置在门户网站。这些观察结果支持一个两态毛细管蒸发模型，准确地描述了状态之间的平衡，自然产生的有效转换压力从模拟观察到的发展。这项工作表明，水化的主机口袋可以调整以下简单的设计规则，预计反过来会影响客体络合的热力学。
Hydrophobic interactions drive the binding of nonpolar ligands to the oily pockets of proteins and supramolecular species in aqueous solution. As such, the wetting of host pockets is expected to play a critical role in determining the thermodynamics of guest binding. Here we use molecular simulations to examine the impact of pressure on the wetting and dewetting of the nonpolar pockets of a series of deep-cavity cavitands in water. The portals to the cavitand pockets are functionalized with both nonpolar (methyl) and polar (hydroxyl) groups oriented pointing either upward or inward toward the pocket. We find wetting of the pocket is favored by the hydroxyl groups and dewetting is favored by the methyl groups. The distribution of waters in the pocket is found to exhibit a two-state-like equilibrium between wet and dry states with a free energy barrier between the two states. Moreover, we demonstrate that the pocket hydration of the cavitands can be collapsed onto a unified adsorption isotherm by assuming the effective pressures within each cavitand pocket differ by a shift pressure that depends on the chemical identity and number of functional groups placed about the portal. These observations support the development of a two-state capillary evaporation model that accurately describes the equilibrium between states and naturally gives rise to the effective shift pressures observed from simulation. This work demonstrates that the hydration of host pockets can be tuned following simple design rules that in turn are expected to impact the thermodynamics of guest complexation.