QM/MM Simulations of Mg and Zn Solvation

Abstract

Mg(II) and Zn(II) ions serve a variety of the biological functions, such as signaling, catalysis, and structure. Despite similar ionic radii (0.72 A for Mg(II) and 0.74 A for Zn(II)), these ions bind to different types of ligands; Mg(II) predominantly binds to phosphates, forming species like Mg-ATP while Zn(II) typically binds to cysteine and histidine side chains. Some of the differences in the biochemistry of Mg(II) and Zn(II) ions are apparent in the solvation energies of these ions in water; despite the similar ionic radii, the hydration free energy of Zn(II) is 30 kcal/mol more favorable than Mg(II). In this work, the hydration properties of Mg(II) and Zn(II) have been explored computationally. The performance in the prediction of the energetics and solvation structure of Mg(II) and Zn(II) are compared. The CHARMM non-polarizable force field incorrectly predicts that Mg(II) has the more favorable solvation free energy. The Drude polarizable model improves the description, but still underestimates the relative solvation energy by 17 kcal/mol. Only a QM/MM simulation using the CHARMM/TURBOMOLE code was able to predict the relative solvation energy and structure of Mg(II) and Zn(II) in good agreement with experiment [1]. ETS-NOCV analysis indicates that this difference is due to increased water-to-ion charge transfer interactions in Zn(II) compare to the Mg(II) due to the higher Lewis acidity of Zn(II).[1] Riahi, S., Roux, B., Rowley, C.N. Can. J. Chem. 2013, 91(7), 552558.