Developing and Assessing Nonbonded Dummy Models of Magnesium Ion with Different Hydration Free Energy References

A large diversity in the targeted
hydration free energies (HFEs)
during model parameterization of metal ions was reported in the literature
with a difference by dozens of kcal/mol. Here, we developed a series
of nonbonded dummy models of the Mg2+ ion targeting different
HFE references in TIP3P water, followed by assessments of the designed
models in the simulations of MgCl2 solution and biological
systems. Together with the comparison of existing models, we conclude
that the difference in the targeted HFEs has a limited influence on
the model performance, while the usability of these models differs
from case to case. The feasibility of reproducing more properties
of Mg2+ such as diffusion constants and water exchange
rates using a nonbonded dummy model is demonstrated. Underestimated
activity derivative and osmotic coefficient of MgCl2 solutions
in high concentration reveal a necessity for further optimization
of ion-pair interactions. The developed dummy models are applicable
to metal coordination with Asp, Glu, and His residues in metalloenzymes,
and the performance in predicting monodentate or bidentate binding
modes of Asp/Glu residues depends on the complexity of metal centers
and the choice of protein force fields. When both the binding modes
coexist, the nonbonded dummy models outperform point charge models,
probably in need of considering polarization of metal-binding residues
by, for instance, charge calibration in classical force fields. This
work is valuable for the use and further development of magnesium
ion models for simulations of metal-containing systems with good accuracy.