Abstract
Water exchange between the first and second hydration shell is essential for the role of Mg2+ in biochemical processes. In order to provide microscopic insights into the exchange mechanism, we resolve the exchange pathways by all-atom molecular dynamics simulations and transition path sampling. Since the exchange kinetics relies on the choice of the water model and the ionic force field, we systematically investigate the influence of seven different polarizable and non-polarizable water and three different Mg2+ models. In all cases, water exchange can occur either via an indirect or direct mechanism (exchanging molecules occupy different/same position on the water octahedron). In addition, the results reveal a crossover from an interchange dissociative (Id) to an associative (Ia) reaction mechanism dependent on the range of the Mg2+-water interaction potential of the respective force field. Standard non-polarizable force fields follow the Id mechanism in agreement with experimental results. By contrast, polarizable and long-ranged non-polarizable force fields follow the Ia mechanism. Our results provide a comprehensive view on the influence of the water model and the ionic force field on the exchange dynamics and the foundation to assess the choice of the force field in biomolecular simulations.
Highlights
In aqueous solutions, Mg2+ ions are surrounded by a hydration shell of six water molecules, which is subsequently enclosed by a second hydration shell
A negative activation volume reflects that the distances and angles are reduced, the exchange occurs inside the first hydration shell, and the mechanism is classified as associative
We show that the exchange occurs outside of the first hydration shell in the dissociative pathways
Summary
Mg2+ ions are surrounded by a hydration shell of six water molecules, which is subsequently enclosed by a second hydration shell. Since water exchange governs any type of reaction involving the replacement of the strongly bound hydration water molecules, resolving the reaction mechanism has received considerable scientific attention in experiments and simulations.. Since water exchange governs any type of reaction involving the replacement of the strongly bound hydration water molecules, resolving the reaction mechanism has received considerable scientific attention in experiments and simulations.6–13 Experimental techniques such as dielectric relaxation, x-ray adsorption, femtosecond mid-infrared, and far-infrared adsorption spectroscopy provide insight into the solvation structure of Mg2+,2,14–16 while nuclear magnetic resonance (NMR) experiments facilitate the direct measurement of water exchange rates.. Still, according to the mechanistic classification for ligand exchange reactions proposed by Langford and Gray, the mechanism can be divided into four categories: associative (A), dissociative (D), interchange associative (Id), and interchange dissociative (Ia) In the former two categories, a detectable intermediate with increased (A) or decreased (D) coordination number exists. A negative activation volume reflects that the distances and angles are reduced, the exchange occurs inside the first hydration shell, and the mechanism is classified as associative.
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