Solvent Fluctuations Induce Non-Markovian Kinetics in Hydrophobic Pocket-Ligand Binding.
Solvent Fluctuations Induce Non-Markovian Kinetics in Hydrophobic Pocket-Ligand Binding.
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DOI：
10.1021/acs.jpcb.6b01219
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
R. G. Weiß;P. Setny;J. Dzubiella
中科院分区：
文献类型：
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作者：
R. G. Weiß;P. Setny;J. Dzubiella
我们通过简约的随机模型系统研究了水波动对疏水配体（键）与疏水袋（锁）结合的键锁关联动力学的影响。后者通过水袋界面的双峰波动描述了袋的集体水合行为，该双峰波动通过疏水相互作用动态耦合到接近配体的扩散运动。这导致由界面位置和配体位置跨越的二维坐标空间中的马尔可夫组过阻尼随机方程。数值模拟证明了配体摩擦力的局部增加、结合动力学的减速以及沿配体反应（距离）坐标的简化一维描述中的局部非马尔可夫（记忆）效应，如先前在显式水模拟中发现的那样。我们的简约模型阐明了局部增强摩擦的起源，可以追溯到空间波动的界面-配体相互作用引起的力-自相关函数的长期衰减。此外，我们构建了配体结合的广义一维朗之万描述，包括反映口袋润湿/去润湿过程的主要频率的空间局部记忆函数，从而能够对我们的结果进行进一步解释和半分析量化。
We investigate the impact of water fluctuations on the key-lock association kinetics of a hydrophobic ligand (key) binding to a hydrophobic pocket (lock) by means of a minimalistic stochastic model system. The latter describes the collective hydration behavior of the pocket by bimodal fluctuations of the water-pocket interface that dynamically couples to the diffusive motion of the approaching ligand via the hydrophobic interaction. This leads to a Markovian set of overdamped stochastic equations in 2D-coordinate-space spanned by the interface position and the ligand position. Numerical simulations demonstrate locally increased friction of the ligand, decelerated binding kinetics, and local non-Markovian (memory) effects in a reduced 1D-description along the ligand's reaction (distance) coordinate as found previously in explicit-water simulations. Our minimalistic model elucidates the origin of locally enhanced friction that can be traced back to long-time decays in the force-autocorrelation function induced by a spatially fluctuating interface-ligand interaction. Furthermore, we construct a generalized 1D-Langevin description of ligand binding including a spatially local memory function that reflects the dominant frequencies of the pocket wetting/dewetting process, enabling further interpretation and a semianalytical quantification of our results.