Kinetic pathways of water exchange in the first hydration shell of magnesium: Influence of water model and ionic force field

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 (I-d) to an associative (I-a) reaction mechanism dependent on the range of the Mg2+-water interaction potential of the respective force field. Standard non-polarizable force fields follow the I-d mechanism in agreement with experimental results. By contrast, polarizable and long-ranged non-polarizable force fields follow the I-a 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.

Automated summary

This study investigates the water exchange mechanism between the hydration shells of Mg2+ through molecular dynamics simulations and transition path sampling. It reveals that the choice of water model and Mg2+ model influences the exchange kinetics, with different mechanisms observed depending on the force field used. The results provide insights into the impact of force field choice on exchange dynamics in biomolecular simulations.