A Kirkwood-Buff derived force field for alkaline earth halide salts

Abstract

The activity and function of many macromolecules in cellular environments are coupled with the binding of divalent ions such as calcium or magnesium. In principle, computer simulations can be used to understand the molecular level aspects of how many important macromolecules interact with ions. However, most of the force fields currently available often fail to accurately reproduce the properties of divalent ions in aqueous environments. Here we develop classical non-polarizable force fields for the aqueous alkaline earth metal halides (MX), where M = Mg, Ca, Sr, Ba and X = Cl, Br, I, which can be used in bimolecular simulations and which are compatible with the Simple Point Charge/Extended (SPC/E) water model. The force field parameters are specifically developed to reproduce the experimental Kirkwood-Buff integrals for aqueous solutions and thereby the experimental activity derivatives, partial molar volumes, and excess coordination numbers. This ensures that a reasonable balance between ion-ion, ion-water, and water-water distributions is obtained. However, this requires a scaling of the cation to water oxygen interaction strength in order to accurately reproduce the integrals. The scaling factors developed for chloride salts are successfully transferable to the bromide and iodide salts. Use of these new models leads to reasonable diffusion constants and dielectric decrements. However, the performance of the models decreases with increasing salt concentration (>4m), and simulations of the pure crystals exhibited unstable behavior.

Formulating rationally via statistical thermodynamics

“…There are reasons as to why the ever-accelerating CPU speed and some potentially gamechanging innovations in free-energy calculations [45] still have not made solubility prediction a relic of the past. Simulations of the liquid state still have to rely on classical molecular dynamics requiring force field parameterization, which is still a matter of active research even for the most common cosolvents (such as urea) for aqueous solutions [46,47].…”

Solvation energies of ions with ensemble cluster-continuum approach

“…For a case of Ca 2+ ion we also performed a classical simulation of one molecule of CaCl 2 in a 99.8 Å box of water, the force field parameters were taken from ref. 68. The simulation step was 2 fs, the temperature of 300 K was controlled by the v-rescale thermostat with coupling time 0.1 ps, the pressure of 1 bar was controlled by the Parrinello-Rahman barostat with coupling time of 2 ps.…”

Kirkwood-Buff integrals from molecular simulation

“…KB integrals can be used for the development and parameterization of force fields [61,108,109]. Weerasinghe and Smith provide KB derived force fields (KBFF) for a number of mixtures such as, sodium chloride in water [108], urea and water [110], acetone and water [111], and methanol and water [112].…”

“…The authors of Refs. [61,108,109] found that macroscopic properties can be accurately computed using the KBFF models, while addressing solute-solute and solvent-solute molecular structure of the systems considered. For instance, in Ref.…”

“…The most important applications of KB integrals will be discussed. KB integrals are being used to study different types of systems from simple, like Lennard-Jones fluids to more complicated systems such as salt solutions [16,41,61,62], alcohol solutions [39,[63][64][65], and biological systems [31]. For such systems, KB integrals can be used to study a number of thermodynamic properties.…”