QM/MM molecular dynamics simulations of the hydration of Mg(II) and Zn(II) ions

Abstract

The hydration of Mg2+ and Zn2+ is examined using molecular dynamics simulations using 3 computational approaches of increasing complexity: the CHARMM nonpolarizable force field based on the TIP3P water model, the Drude polarizable force field based on the SWM4-NDP water model, and a combined QM/MM approach in which the inner coordination sphere is represented using a high-quality density functional theory (DFT) model (PBE/def2-TZVPP), and the remainder of the bulk water solvent is represented using the polarizable SWM4-NDP water model. The characteristic structural distribution functions (radial, angular, and tilt) are comparedand show very good agreement between the polarizable force field and QM/MM approaches. They predict an average Mg–O distance of 2.11 Å and an Zn–O distance of 2.13 Å, in good agreement with the available experimental neutron scattering and EXAFS data, while the Mg–O distances calculated using the nonpolarizable force field are 0.1 Å too short. Mg2+ (aq) and Zn2+ (aq) both have a coordination number of 6 and have a remarkably similar octahedral coordination mode, despite the chemical differences between these ions. Thermodynamic integration was used to calculate the relative hydration free energies of these ions (ΔΔGhydr). The nonpolarizable model is in error by 60 kcal mol– 1 and incorrectly predicts that Mg2+ has the more negative hydration energy. The Drude polarizable model predicts a ΔΔGhydr of only –13.2 kcal kcal mol– 1, an improvement over the results of the nonpolarizable force field, but still signficantly different than the experimental value of –30.1 kcal mol–1. The combined QM/MM approach performs much better, predicting a ΔΔGhydr of –34.8 kcal mol–1 in excellent agreement with experiment. These calculations support the experimental observation that Zn2+ has more favourable solvation free energy than Mg2+ despite having a very similar solvation structure.