溶剂波动诱导疏水口袋-配体结合的非马尔可夫动力学
Solvent fluctuations induce non-Markovian kinetics in hydrophobic pocket-ligand binding
摘要：
我们研究了水的波动对疏水配体（钥匙）结合到疏水口袋（锁）的键锁缔合动力学的影响，通过一个最小的随机模型系统。它描述了集体水合行为的口袋由双峰波动的水口袋界面，动态耦合到扩散运动的接近配体通过疏水相互作用。这导致了一组过阻尼朗之万方程在二维坐标空间，这是马尔可夫在每个维度。数值模拟表明，局部增加摩擦的配位体，减速结合动力学，和局部非马尔可夫（记忆）效应的配位体的反应坐标中发现以前在显式水分子动力学研究模型疏水口袋配位体结合[1，2]。我们的最低限度的模型阐明了起源的有效增强摩擦的过程中，可以追溯到长时间的衰减的力自相关函数引起的有效的，空间波动的口袋配体相互作用。此外，我们构建了一个广义的1D-Langevin描述，包括一个空间本地的记忆功能，使进一步的解释和半分析量化的结果耦合的2D系统。
英文摘要：
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. It describes the collective hydration behavior of the pocket by bimodal fluctuations of a water-pocket interface that dynamically couples to the diffusive motion of the approaching ligand via the hydrophobic interaction. This leads to a set of overdamped Langevin equations in 2D-coordinate-space, that is Markovian in each dimension. Numerical simulations demonstrate locally increased friction of the ligand, decelerated binding kinetics, and local non-Markovian (memory) effects in the ligand's reaction coordinate as found previously in explicit-water molecular dynamics studies of model hydrophobic pocket-ligand binding [1,2]. Our minimalistic model elucidates the origin of effectively enhanced friction in the process that can be traced back to long-time decays in the force-autocorrelation function induced by the effective, spatially fluctuating pocket-ligand interaction. Furthermore, we construct a generalized 1D-Langevin description including a spatially local memory function that enables further interpretation and a semi-analytical quantification of the results of the coupled 2D-system.
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