Polarizable molecular dynamics simulation of Zn(II) in water using the AMOEBA force field

The hydration free energy, structure, and dynamics of the zinc divalent cation are studied using a polarizable force field in molecular dynamics simulations. Parameters for the Zn²⁺are derived from gas-phase ab initio calculation of the Zn²⁺-water dimer. The Thole-based dipole polarization is adjusted on the basis of the constrained space orbital variations (CSOV) calculation, while the symmetry adapted perturbation theory (SAPT) approach is also discussed. The vdW parameters of Zn²⁺ have been obtained by comparing the AMOEBA Zn²⁺-water dimerization energy with results from several theory levels and basis sets over a range of distances. Molecular dynamics simulations of Zn²⁺ solvation in bulk water are subsequently performed with the polarizable force field. The calculated first-shell water coordination number, water residence time, and free energy of hydration are consistent with experimental and previous theoretical values. The study is supplemented with extensive reduced variational space (RVS) and electron localization function (ELF) computations in order to unravel the nature of the bonding in Zn²⁺ (H₂O)n (n ) 1, 6) complexes and to analyze the charge transfer contribution to the complexes. Results show that the importance of charge transfer decreases as the size of the Zn-water cluster grows due to anticooperativity and to changes in the nature of the metal-ligand bonds. Induction could be dominated by polarization when the system approaches the condensed phase and the covalent effects are eliminated from the Zn(II)-water interaction. To construct an "effective" classical polarizable potential for Zn²⁺ in bulk water, one should therefore avoid overfitting to the ab initio charge transfer energy of the Zn ²⁺-water dimer. Indeed, in order to avoid overestimation of the condensed-phase many-body effects, which is crucial to the transferability of polarizable molecular dynamics, charge transfer should not be included within the classical polarization contribution and should preferably be either incorporated into the pairwise van der Waals contribution or treated explicitly.