Solvent Fluctuations Induce Non-Markovian Kinetics in Hydrophobic Pocket-Ligand Binding

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• 作者：R. Gregor Weiß ; Piotr Setny ; Joachim Dzubiella
• 刊名：Journal of Physical Chemistry B
• 出版年：2016
• 出版时间：August 25, 2016
• 年：2016
• 卷：120
• 期：33
• 页码：8127-8136
• 全文大小：488K
• 年卷期：0
• ISSN：1520-5207

文摘

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.