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.

中文翻译：

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带有移动质子的经典分子动力学

标准经典分子动力学模拟的一个重要限制是无法建立或破坏化学键。这严重限制了我们研究甚至涉及最简单的化学反应（质子转移）的过程的能力。现有的在经典力学的背景下允许质子转移的方法相当麻烦，并且尚未获得广泛的使用和常规地位。在这里，我们重新考虑了分子动力学与周期性随机质子跃迁的结合。为了确保计算效率，我们提出了一个非玻耳兹曼接受准则，该准则可以通过启发式调整来维持不同质子化状态和质子转移速率之间的正确或理想的热力学平衡。提出了水合氢，Asp，Glu和His的参数。该算法在CHARMM程序中实现，并测试了质子在大量水和碳纳米管中的扩散以及质子传递蛋白A通道中的质子电导。使用从散装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，并给出了对短杆菌肽A中质子电导率的合理估计。