QM/MM Molecular Dynamics Simulations of the Hydration of Mg(II) and Zn(II) Ions

The hydration of Mg and Zn is examined using molecular dynamics simulations using three computational approaches of increasing complexity: the CHARMM non-polarizable 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/def2TZVPP) 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 compared, which 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 non-polarizable force field are 0.1 Å too short. Mg(aq) and Zn(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 (∆∆Ghydr). The non-polarizable model is in error by 60 kcal mol−1 and incorrectly predicts that Mg has the more negative hydration energy. The Drude polarizable model predicts a ∆∆Ghydr of only –13.2 kcal mol−1, an improvement over the results of the non-polarizable 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 ∆∆Ghydr of –34.8 kcal mol−1 in excellent agreement with experiment. These calculations support the experimental observation that Zn has more favourable solvation free energy than Mg despite having a very similar solvation structure.