水辅助质子通过蛋白质和其他密闭空间的定量范例

Chenghan Li, G. Voth
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引用次数: 12

摘要

正如Grotthuss在200多年前首次提出的那样,质子传输是通过化学断键和成键质子跳跃机制通过水网络或“线”实现的,这些水网络或“线”通常包含在蛋白质通道或纳米管等受限系统中。本文利用图论的概念来定义水线连通性和质子易输运的连续可微集体变量。因此,水的连通性可以通过自由能采样来明确量化,从而定性和定量地描述水促进质子通过Grotthuss跳跃的热力学和动力学,这是自自然界中这一关键化学过程的第一次概念识别以来一直缺乏的东西。水辅助质子在密闭空间中的传输影响着生物分子和纳米材料系统中的许多现象。在这种情况下,在受限通道中波动的水分子为水合过剩质子通过Grotthuss穿梭迁移提供了环境和介质。然而,一个明确的集体变量(CV),准确地耦合水合作用和质子线连通性与质子易位仍然是难以捉摸的。为了解决这一重要挑战,并因此定义了一个在有限空间中质子传输的定量范式,本研究从图论中推导了一个CV,该CV被验证可以准确地描述与碳纳米管和Cl - /H+反转运蛋白(Cl -ec1)中质子易位相关的水丝形成和断裂。引入多余的质子后,发现水线的构象和热力学发生了重大变化。根据新的CV,当水线被定义为断连时,在质子易位自由能谱中发现了巨大的障碍,即使相关的受限空间仍然相当水合,并且通过水结构存在的简单测量,质子传输将通过过度简化的测量被预测为容易的。然而,在这个范例中,水的简单存在不足以推断质子的移位,因为多余的质子本身能够驱动水合作用,此外,水分子本身必须充分连接以促进任何成功的质子运输。
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A quantitative paradigm for water-assisted proton transport through proteins and other confined spaces
Significance As first proposed more than 200 y ago by Grotthuss, proton transport is enabled by a chemical bond-breaking and bond-making proton-hopping mechanism through water networks or “wires,” often contained within confined systems such as protein channels or nanotubes. Herein, concepts from graph theory are utilized in order to define a continuously differentiable collective variable for water wire connectivity and facile proton transport. As such, the water connectivity can be explicitly quantified via free-energy sampling to both qualitatively and quantitatively describe the thermodynamics and kinetics of water-facilitated proton transport via Grotthuss hopping—something that has been lacking since the first conceptual identification of this key chemical process in nature. Water-assisted proton transport through confined spaces influences many phenomena in biomolecular and nanomaterial systems. In such cases, the water molecules that fluctuate in the confined pathways provide the environment and the medium for the hydrated excess proton migration via Grotthuss shuttling. However, a definitive collective variable (CV) that accurately couples the hydration and the connectivity of the proton wire with the proton translocation has remained elusive. To address this important challenge—and thus to define a quantitative paradigm for facile proton transport in confined spaces—a CV is derived in this work from graph theory, which is verified to accurately describe water wire formation and breakage coupled to the proton translocation in carbon nanotubes and the Cl−/H+ antiporter protein, ClC-ec1. Significant alterations in the conformations and thermodynamics of water wires are uncovered after introducing an excess proton into them. Large barriers in the proton translocation free-energy profiles are found when water wires are defined to be disconnected according to the new CV, even though the pertinent confined space is still reasonably well hydrated and—by the simple measure of the mere existence of a water structure—the proton transport would have been predicted to be facile via that oversimplified measure. In this paradigm, however, the simple presence of water is not sufficient for inferring proton translocation, since an excess proton itself is able to drive hydration, and additionally, the water molecules themselves must be adequately connected to facilitate any successful proton transport.
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