Pomès R, Roux B
Departement de Physique, Université de Montréal, Québec, Canada.
Biophys J. 1996 Jul;71(1):19-39. doi: 10.1016/S0006-3495(96)79211-1.
The rapid translocation of H+ along a chain of hydrogen-bonded water molecules, or proton wire, is thought to be an important mechanism for proton permeation through transmembrane channels. Computer simulations are used to study the properties of the proton wire formed by the single-file waters in the gramicidin A channel. The model includes the polypeptidic dimer, with 22 water molecules and one excess proton. The dissociation of the water molecules is taken into account by the "polarization model" of Stillinger and co-workers. The importance of quantum effects due to the light mass of the hydrogen nuclei is examined with the use of discretized Feynman path integral molecular dynamics simulations. Results show that the presence of an excess proton in the pore orients the single-file water molecules and affects the geometry of water-water hydrogen bonding interactions. Rather than a well-defined hydronium ion OH3+ in the single-file region, the protonated species is characterized by a strong hydrogen bond resembling that of O2H5+. The quantum dispersion of protons has a small but significant effect on the equilibrium structure of the hydrogen-bonded water chain. During classical trajectories, proton transfer between consecutive water molecules is a very fast spontaneous process that takes place in the subpicosecond time scale. The translocation along extended regions of the chain takes place neither via a totally concerted mechanism in which the donor-acceptor pattern would flip over the entire chain in a single step, nor via a succession of incoherent hops between well-defined intermediates. Rather, proton transfer in the wire is a semicollective process that results from the subtle interplay of rapid hydrogen-bond length fluctuations along the water chain. These rapid structural fluctuations of the protonated single file of waters around an average position and the slow movements of the average position of the excess proton along the channel axis occur on two very different time scales. Ultimately, it is the slow reorganization of hydrogen bonds between single-file water molecules and channel backbone carbonyl groups that, by affecting the connectivity and the dynamics of the single-file water chain, also limits the translocation of the proton across the pore.
氢离子沿着由氢键连接的水分子链（即质子线）快速迁移，被认为是质子透过跨膜通道的一种重要机制。计算机模拟被用于研究短杆菌肽A通道中由单列水分子形成的质子线的性质。该模型包括多肽二聚体、22个水分子和一个额外的质子。水分子的解离通过斯蒂林格及其同事的“极化模型”来考虑。利用离散化的费曼路径积分分子动力学模拟来研究由于氢原子核质量轻而产生的量子效应的重要性。结果表明，孔中额外质子的存在使单列水分子定向，并影响水分子间氢键相互作用的几何结构。在单列区域中，质子化物种并非明确的水合氢离子OH3+，而是以类似于O2H5+的强氢键为特征。质子的量子弥散对氢键连接的水链的平衡结构有微小但显著的影响。在经典轨迹中，相邻水分子间的质子转移是一个非常快速的自发过程，发生在亚皮秒时间尺度内。沿着链的延伸区域的迁移既不是通过完全协同的机制，即供体 - 受体模式在一步中翻转整个链，也不是通过在明确中间体之间的一系列非相干跳跃。相反，质子线中的质子转移是一个半集体过程，它源于沿着水链的快速氢键长度波动的微妙相互作用。质子化单列水分子围绕平均位置的这些快速结构波动以及额外质子的平均位置沿着通道轴的缓慢移动发生在两个非常不同的时间尺度上。最终，正是单列水分子与通道主链羰基之间氢键的缓慢重组，通过影响单列水链的连通性和动力学，也限制了质子穿过孔的迁移。
