多维偏置在加速动力学中的优势：应用于乙酸酸解离常数 $pK_a$ 的计算
Advantages of multi-dimensional biasing in accelerated dynamics: application to the calculation of the acid $pK_a$ for acetic acid
AI总结：
针对 ReaxFF 模拟乙酸去质子化时单一配位数 CV 导致 $K_a$ 随盒子尺寸变化的问题，引入离子距离作为第二 CV，实现多维偏置并提升采样效率、消除尺寸依赖。
摘要：
诸如 metadynamics（元动力学）之类的加速采样方法，在涉及稀有事件的计算中已显示出显著优势；否则，要确定这些事件就需要采样数量多到令人却步的构型，例如确定两个或多个化学上不同状态之间的自由能差，酸解离常数 $K_a$ 的计算便属于此类情形。在这种情况下，最常用的方法是通过单个集体变量（CV）对系统施加偏置，该变量表示质子供体基团的 $coordination~number$（配位数），所得结果与实验具有合理的一致性。本文中，我们使用反应力场 ReaxFF 研究乙酸的去质子化，并观察到当仅对配位数 CV 施加偏置时，$K_a$ 对模拟盒子尺寸存在显著依赖；这是由于小模拟系统对去质子化状态的采样不充分，而较大系统的采样效率低下。引入第二个表示 H$_3$O$^+$ 阳离子与乙酸根阴离子之间距离的 CV，可带来显著更高的采样效率，既加速了动力学，又实际上消除了对计算盒子尺寸的依赖。
英文摘要：
The use of accelerated sampling methods such as metadynamics has shown significant advantage in calculations that involve infrequent events, which would otherwise require sampling a prohibitive number of configurations to determine, e.g., difference in free energies between two or more chemically distinct states such as in the calculation of acid dissociation constants $K_a$. In this case, the most common method is to bias the system via a single collective variable (CV) representing the $coordination~number$ of the proton donor group, which yields results in reasonable agreement with experiments. Here we study the deprotonation of acetic acid using the reactive force field ReaxFF and observe a significant dependence of $K_a$ on the simulation box size when biasing only the coordination number CV, which is due to incomplete sampling of the deprotonated state for small simulation systems, and inefficient sampling for larger ones. Incorporating a second CV representing the distance between the H$_3$O$^+$ cation and the acetate anion results in a substantially more efficient sampling both accelerating the dynamics and virtually eliminating the computational box size dependence.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
