Grand canonical Monte Carlo (GCMC) simulations of ionic solutions with explicit solvent models are known to be challenging. One challenge arises from the treatment of long-range electrostatics and finite-box size in Monte Carlo simulations when periodic boundary condition and Ewald summation methods are used. Another challenge is that constant excess chemical potential GCMC simulations for charged solutes suffer from inadequate insertion and deletion acceptance ratios. In this work, we address those problems by implementing an oscillating excess chemical potential GCMC algorithm with smooth particle mesh Ewald and finite-box-size corrections to treat the long-range electrostatics. The developed GCMC simulation program was combined with GROMACS to perform GCMC/MD simulations of ionic solutions individually containing Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺, F^–, Cl^–, Br^–, I^–, Ca²⁺, and Mg²⁺, respectively. Our simulation results show that the combined GCMC/MD approach can approximate the ionic hydration free energies with proper treatment of long-range electrostatics. Our developed simulation approach can open up new avenues for simulating complex chemical and biomolecular systems and for drug discovery.

中文翻译：

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大正则蒙特卡罗/分子动力学模拟在水中测定离子水合自由能

众所周知，使用显式溶剂模型对离子溶液进行大规范蒙特卡洛（GCMC）模拟具有挑战性。当使用周期性边界条件和Ewald求和方法时，在Monte Carlo模拟中对远程静电和有限盒大小的处理引起了一个挑战。另一个挑战是，带电溶质的不断过量化学势GCMC模拟存在插入和缺失接受率不足的问题。在这项工作中，我们通过使用具有平滑粒子网格Ewald的振动超化学势GCMC算法和有限箱尺寸校正来处理长距离静电，来解决这些问题。将开发的GCMC模拟程序与GROMACS结合使用，对分别包含Li ⁺的离子溶液进行GCMC / MD模拟，钠⁺，K ⁺，RB ⁺，铯⁺，F ^{- ，}氯^- ，溴^- ，我^- ，钙²⁺和Mg ²⁺分别。我们的仿真结果表明，采用GCMC / MD组合方法可以适当地处理远距离静电，从而近似于离子水合自由能。我们开发的模拟方法可以为模拟复杂的化学和生物分子系统以及药物开发开辟新途径。