Multisite Ion Model in Concentrated Solutions of Divalent Cations (MgCl₂ and CaCl₂): Osmotic Pressure Calculations

Abstract

Accurate force field parameters for ions are essential for meaningful simulation studies of proteins and nucleic acids. Currently accepted models of ions, especially for divalent ions, do not necessarily reproduce the right physiological behavior of Ca2+ and Mg2+ ions. Saxena and Sept (J. Chem. Theor. Comput.2013, 9, 3538–3542) described a model, called the multisite-ion model, where instead of treating the ions as an isolated sphere, the charge was split into multiple sites with partial charge. This model provided accurate inner shell coordination of the ion with biomolecules and predicted better free energies for proteins and nucleic acids. Here, we expand and refine the multisite model to describe the behavior of divalent ions in concentrated MgCl2 and CaCl2 electrolyte solutions, eliminating the unusual ion–ion pairing and clustering of ions which occurred in the original model. We calibrate and improve the parameters of the multisite model by matching the osmotic pressure of concentrated solutions of MgCl2 to the experimental values and then use these parameters to test the behavior of CaCl2 solutions. We find that the concentrated solutions of both divalent ions exhibit the experimentally observed behavior with correct osmotic pressure, the presence of solvent separated ion pairs instead of direct ion pairs, and no aggregation of ions. The improved multisite model for (Mg2+ and Ca2+) can be used in classical simulations of biomolecules at physiologically relevant salt concentrations.

Ion association characteristics in MgCl2and CaCl2aqueous solutions: a density functional theory and molecular dynamics investigation

“…In the work of Zhu et al [57], the ion association in MgCl 2 solution is much less obviously than that in CaCl 2 solution. Compared with the results of Zhu et al, the situation is reversed, which also agrees with the MD results of Saxena [25]. Since the constraint on the first hydration shell of Mg 2 + is strong, 0.25 ns may be not enough for relaxation, and thus the ion association was underestimated in the work of Zhu et al B3LYP/aVDZ results of MgCl 2 (H 2 O) n (n = 5-10) clusters show that ion associated species are slightly less favourable.…”

“…The recent work of Jungwirth et al also indicated the formation of ion-associated species in 4.0 mol/kg CaCl 2 aqueous solution using classical MD simulations [24]. Whereas, osmotic pressure calculations of Sasena et al [25] exhibited SSIP with double Cl − dissociated (SSIP/d, [Ca(H 2 O) 6 Cl 2 ] 0 ,) structures instead of CIP structures exist in 0.1-3.0 mol/kg CaCl 2 electrolyte solutions. It seems that CIP structures cannot be easily detected even in concentrated CaCl 2 aqueous solution.…”

Osmotic pressure of aqueous electrolyte solutions via molecular simulations of chemical potentials: Application to NaCl

“…FFs determined by these means have frequently been unable to satisfactorily predict more complex and composition-dependent thermodynamic properties, and thus the composition dependence of solution chemical potentials [44], and the osmotic pressure, [35,24,34,56], ˘, have recently been used as alternative approaches to fit FF parameters.…”

Generalized Manning Condensation Model Captures the RNA Ion Atmosphere

“…Explicit solvent simulations appear to underpredict Γ 2+ , possibly because K + can dehydrate too easily [41] and drive away Mg 2+ . Many ion parameters have been proposed for explicit solvent simulation [42–45]. The excess Mg 2+ is a sensitive measure of RNA electrostatics that may be useful in future calibration of explicit solvent ion parameters.…”