Structure and Thermodynamics of Mg:Phosphate Interactions in Water: A Simulation Study

Abstract

The association of Mg(2+) and H2 PO4 (-) in water can give insights into Mg:phosphate interactions in general, which are very widespread, but for which experimental data is surprisingly sparse. It is studied through molecular dynamics simulations (>100 ns) by using the polarizable AMOEBA force field, and the association free energy is computed for the first time. Explicit consideration of outer-sphere and two types of inner-sphere association provides considerable insight into the dynamics and thermodynamics of ion pairing. After careful assessment of the computational approximations, the agreement with experimental values indicates that the methodology can be extended to other inorganic and biological Mg:phosphate interactions in solution.

Classical Drude Polarizable Force Field Model for Methyl Phosphate and Its Interactions with Mg2+

“…The OS lifetime is roughly comparable to the rate of OS/unbound transitions obtained for normalPi- with the Amoeba force field (which was not measured precisely). 14…”

“…4), which was shown earlier to predominate. 14 For normalPi2-, we also considered OS binding. For MP 2− , we considered both OS and Inner Sphere binding (IS; Mg 2+ directly coordinates the phosphate).…”

Binding of Divalent Cations to Aqueous Acetate: Molecular Simulations Guided by Raman Spectroscopy

“…〉, numerically estimated on the fully coupled simulation window. 73 Finally, the standard binding free energy is obtained as ΔG bind o = ΔG1 -ΔG2 + ΔGPBC + ΔGrestr + ΔGunrestr. Note that the correction term (ΔGPBC + ΔGrestr + ΔGunrestr) is here overall of the same magnitude as the raw free energy difference, and it is thus crucial to properly take it into account.…”

Binding of Divalent Cations to Aqueous Acetate: Molecular Simulations Guided by Raman Spectroscopy

“…The free-energy contribution of this restraint needs to be carefully accounted for both in the coupled and the uncoupled state. [69][70][71] In the uncoupled state, the free energy of applying the restraint with respect to the standard state concentration can be expressed and numerically estimated as Δ "#$%" = ∫ 4 & e '() !"#$! (+) dr -.…”

“…Several schemes have been suggested to correct this limitation, either through explicit inclusion of electronic polarization with the development of fully polarizable force fields (e.g. 69,[92][93][94][95] ), or through a mean-field approach, the Electronic Continuum Correction, [55][56][57]59 that suggests to implicitly account for electronic polarization by scaling the charge of charged moieties by a factor of 1/>ε el = 0.75, where εel = 1.78 is the electronic part of the water dielectric constant. A milder factor 0.8 has also been tested as an attempt to compensate the fact water models have a dielectric constant that already contains more than pure nuclear polarization (see Methods).…”