Optimized Magnesium Force Field Parameters for Biomolecular Simulations with Accurate Solvation, Ion-Binding, and Water-Exchange Properties in SPC/E, TIP3P-fb, TIP4P/2005, TIP4P-Ew, and TIP4P-D

Magnesium is essential in many vital processes. To correctly describe Mg2+ in physiological processes by molecular dynamics simulations, accurate force fields are fundamental. Despite the importance, force fields based on the commonly used 12-6 Lennard-Jones potential showed significant shortcomings. Recently progress was made by an optimization procedure that implicitly accounts for polarizability. The resulting microMg and nanoMg force fields (J. Chem. Theory Comput. 2021, 17, 2530-2540) accurately reproduce a broad range of experimental solution properties and the binding affinity to nucleic acids in TIP3P water. Since countless simulation studies rely on available water models and ion force fields, we here extend the optimization and provide Mg2+ parameters in combination with the SPC/E, TIP3P-fb, TIP4P/2005, TIP4P-Ew, and TIP4P-D water models. For each water model, the Mg2+ force fields reproduce the solvation free energy, the distance to oxygens in the first hydration shell, the hydration number, the activity coefficient derivative in MgCl2 solutions, and the binding affinity and distance to the phosphate oxygens on nucleic acids. We present two parameter sets: MicroMg yields water exchange on the microsecond time scale and matches the experimental exchange rate. Depending on the water model, nanoMg yields accelerated water exchange in the range of 10(6) to 10(8) exchanges per second. The nanoMg parameters can be used to enhance the sampling of binding events, to obtain converged distributions of Mg2+, or to predict ion binding sites in biomolecular simulations. The parameter files are freely available at https://github.com/bio-phys/optimizedMgFFs.

Automated summary

Research has made progress in accurately simulating magnesium ions in physiological processes through optimized force fields, providing a new approach to address the shortcomings of existing 12-6 Lennard-Jones potential force fields. These parameters can accurately reproduce experimental results in various water models.