Water exchange between the first and second hydration shell is essential for the role of Mg²⁺ in biochemical processes. In order to provide microscopic insights into the exchange mechanism, we resolve the exchange pathways by all-atom molecular dynamics simulations and transition path sampling. Since the exchange kinetics relies on the choice of the water model and the ionic force field, we systematically investigate the influence of seven different polarizable and non-polarizable water and three different Mg²⁺ models. In all cases, water exchange can occur either via an indirect or direct mechanism (exchanging molecules occupy different/same position on water octahedron). In addition, the results reveal a crossover from an interchange dissociative (I_d) to an associative (I_a) reaction mechanism dependent on the range of the Mg²⁺-water interaction potential of the respective force field. Standard non-polarizable force fields follow the I_d mechanism in agreement with experimental results. By contrast, polarizable and long-ranged non-polarizable force fields follow the I_a mechanism. Our results provide a comprehensive view on the influence of the water model and ionic force field on the exchange dynamics and the foundation to assess the choice of the force field in biomolecular simulations.

中文翻译：

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镁第一水合壳中水交换的动力学途径：水模型和离子力场的影响

第一和第二水合壳层之间的水交换对于 Mg ²⁺在生化过程中的作用至关重要。为了提供对交换机制的微观见解，我们通过全原子分子动力学模拟和跃迁路径采样解析了交换途径。由于交换动力学依赖于水模型和离子力场的选择，我们系统地研究了七种不同的极化和非极化水以及三种不同的 Mg ²⁺模型的影响。在所有情况下，水交换可以通过间接或直接机制发生（交换分子在水八面体上占据不同/相同的位置）。此外，结果揭示了一个交换分离的交叉（I _d) 到缔合 (I _a ) 反应机制，取决于相应力场的 Mg ^{2+ -}水相互作用势的范围。标准的不可极化力场遵循 I _d机制，与实验结果一致。相比之下，可极化和远程非极化力场遵循 I _a机制。我们的结果提供了关于水模型和离子力场对交换动力学的影响的全面观点，并为评估生物分子模拟中力场的选择奠定了基础。