Lazaridis Themis, Hummer Gerhard
Department of Chemistry, City College of New York/CUNY , 160 Convent Avenue, New York, New York 10031, United States.
Graduate Programs in Chemistry, Biochemistry & Physics, Graduate Center, City University of New York , 365 Fifth Ave, New York, New York 10016, United States.
J Chem Inf Model. 2017 Nov 27;57(11):2833-2845. doi: 10.1021/acs.jcim.7b00603. Epub 2017 Nov 14.
An important limitation of standard classical molecular dynamics simulations is the inability to make or break chemical bonds. This restricts severely our ability to study processes that involve even the simplest of chemical reactions, the transfer of a proton. Existing approaches for allowing proton transfer in the context of classical mechanics are rather cumbersome and have not achieved widespread use and routine status. Here we reconsider the combination of molecular dynamics with periodic stochastic proton hops. To ensure computational efficiency, we propose a non-Boltzmann acceptance criterion that is heuristically adjusted to maintain the correct or desirable thermodynamic equilibria between different protonation states and proton transfer rates. Parameters are proposed for hydronium, Asp, Glu, and His. The algorithm is implemented in the program CHARMM and tested on proton diffusion in bulk water and carbon nanotubes and on proton conductance in the gramicidin A channel. Using hopping parameters determined from proton diffusion in bulk water, the model reproduces the enhanced proton diffusivity in carbon nanotubes and gives a reasonable estimate of the proton conductance in gramicidin A.
标准经典分子动力学模拟的一个重要局限性在于无法形成或断裂化学键。这严重限制了我们研究甚至涉及最简单化学反应（质子转移）过程的能力。在经典力学背景下允许质子转移的现有方法相当繁琐，尚未得到广泛应用和常规使用。在此，我们重新考虑分子动力学与周期性随机质子跳跃的结合。为确保计算效率，我们提出一种非玻尔兹曼接受准则，该准则经过启发式调整，以维持不同质子化状态和质子转移速率之间正确或理想的热力学平衡。针对水合氢离子、天冬氨酸、谷氨酸和组氨酸提出了参数。该算法在CHARMM程序中实现，并在体相水和碳纳米管中的质子扩散以及短杆菌肽A通道中的质子传导方面进行了测试。使用从体相水中质子扩散确定的跳跃参数，该模型再现了碳纳米管中增强的质子扩散率，并对短杆菌肽A中的质子传导给出了合理估计。
