Braun-Sand Sonja, Burykin Anton, Chu Zhen Tao, Warshel Arieh
University of Southern California, Los Angeles, California 90089, USA.
J Phys Chem B. 2005 Jan 13;109(1):583-92. doi: 10.1021/jp0465783.
The nature of proton transduction (PTR) through a file of water molecules, along the gramicidin A (gA) channel, has long been considered as being highly relevant to PTR in biological systems. Previous attempts to model this process implied that the so-called Grotthuss mechanism and the corresponding orientation of the water file plays a major role. The present work reexamines the PTR in gA by combining a fully microscopic empirical valence bond (EVB) model and a recently developed simplified EVB-based model with Langevin dynamics (LD) simulations. The full model is used first to evaluate the free energy profile for a stepwise PTR process. The corresponding results are then used to construct the effective potential of the simplified EVB. This later model is then used in Langevin dynamics simulations, taking into account the correct physics of possible concerted motions and the effect of the solvent reorganization. The simulations reproduce the observed experimental trend and lead to a picture that is quite different from that assumed previously. It is found that the PTR in gA is controlled by the change in solvation energy of the transferred proton along the channel axis. Although the time dependent electrostatic fluctuations of the channel and water dipoles play their usual role in modulating the proton-transfer process (Proc. Natl. Acad. Sci. U.S.A. 1984, 81, 444), the PTR rate is mainly determined by the free energy profile. Furthermore, the energetics of the reorientation of the unprotonated water file do not appear to provide a consistent way of assessing the activation barrier for the PTR process. It seems to us that in the case of gA, and probably other systems with significant electrostatic barriers for the transfer of the proton charge, the PTR rate is controlled by the electrostatic barrier. This finding has clear consequences with regards to PTR processes in biological systems.
长期以来，人们一直认为质子通过沿短杆菌肽A（gA）通道排列的水分子链进行转导（PTR）的性质与生物系统中的质子转导高度相关。此前对该过程进行建模的尝试表明，所谓的Grotthuss机制以及水分子链的相应取向起着主要作用。本研究通过结合全微观经验价键（EVB）模型和最近开发的基于EVB的简化模型与朗之万动力学（LD）模拟，重新审视了gA中的质子转导。首先使用完整模型评估逐步质子转导过程的自由能分布。然后将相应结果用于构建简化EVB的有效势。随后将该模型用于朗之万动力学模拟，同时考虑了可能协同运动的正确物理机制以及溶剂重组的影响。模拟结果再现了观察到的实验趋势，并得出了与先前假设截然不同的图景。研究发现，gA中的质子转导受沿通道轴转移质子的溶剂化能变化控制。尽管通道和水偶极子随时间变化的静电涨落在调节质子转移过程中发挥着通常的作用（《美国国家科学院院刊》1984年，81卷，444页），但质子转导速率主要由自由能分布决定。此外，未质子化水分子链重新取向的能量学似乎并未提供一种评估质子转导过程活化能垒的一致方法。在我们看来，对于gA以及可能其他存在显著质子电荷转移静电势垒的系统，质子转导速率受静电势垒控制。这一发现对于生物系统中的质子转导过程具有明确的影响。
