Charge scaling, also denoted as the electronic continuum correction, has proven to be an efficient method for effectively including electronic polarization in force field molecular dynamics simulations without additional computational costs. However, scaling charges in existing force fields, fitted at least in part to experimental data, lead to inconsistencies, such as overscaling. We have, therefore, recently developed a four-site water model consistent with charge scaling, i.e., possessing the correct low-frequency dielectric constant of 45. Here, we build on top of this water model to develop charge-scaled models of biologically relevant Li+, Na+, K+, Ca2+, and Mg2+ cations as well as Cl-, Br-, and I- anions, employing machine learning to streamline and speed up the parametrization process. On the one hand, we show that the present model outperforms the best existing charge scaled model of aqueous ions. On the other hand, the present work points to a future need for consistently and simultaneously improving the water and ion models within the electronic continuum correction framework.

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Flemingovo nam 2 Prague 6 CZ 16610 Czech Republic

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Leontyev I. V., Stuchebrukhov A. A.. Electronic Continuum Model for Molecular Dynamics Simulations of Biological Molecules. J. Chem. Theory Comput. 2010;6(5):1498–1508. doi: 10.1021/ct9005807. PubMed DOI PMC

Leontyev I., Stuchebrukhov A.. Accounting for electronic polarization in non-polarizable force fields. Phys. Chem. Chem. Phys. 2011;13(7):2613–2626. doi: 10.1039/c0cp01971b. PubMed DOI

Kirby B. J., Jungwirth P.. Charge Scaling Manifesto: A Way of Reconciling the Inherently Macroscopic and Microscopic Natures of Molecular Simulations. J. Phys. Chem. Lett. 2019;10(23):7531–7536. doi: 10.1021/acs.jpclett.9b02652. PubMed DOI

Duboué-Dijon E., Javanainen M., Delcroix P., Jungwirth P., Martinez-Seara H.. A practical guide to biologically relevant molecular simulations with charge scaling for electronic polarization. J. Chem. Phys. 2020;153(5):050901. doi: 10.1063/5.0017775. PubMed DOI

Kohagen M., Mason P. E., Jungwirth P.. Accurate Description of Calcium Solvation in Concentrated Aqueous Solutions. J. Phys. Chem. B. 2014;118(28):7902–7909. doi: 10.1021/jp5005693. PubMed DOI

Mason P. E., Ansell S., Neilson G. W., Rempe S. B.. Neutron Scattering Studies of the Hydration Structure of Li+ J. Phys. Chem. B. 2015;119(5):2003–2009. doi: 10.1021/jp511508n. PubMed DOI

Duboué-Dijon E., Mason P. E., Fischer H. E., Jungwirth P.. Hydration and Ion Pairing in Aqueous Mg2+ and Zn2 Solutions: Force-Field Description Aided by Neutron Scattering Experiments and Ab Initio Molecular Dynamics Simulations. J. Phys. Chem. B. 2018;122(13):3296–3306. doi: 10.1021/acs.jpcb.7b09612. PubMed DOI

Martinek T., Duboué-Dijon E., Timr Š., Mason P. E., Baxová K., Fischer H. E., Schmidt B., Pluhařová E., Jungwirth P.. Calcium ions in aqueous solutions: Accurate force field description aided by ab initio molecular dynamics and neutron scattering. J. Chem. Phys. 2018;148(22):222813. doi: 10.1063/1.5006779. PubMed DOI

Berendsen, H. J. C. ; Postma, J. P. M. ; van Gunsteren, W. F. ; Hermans, J. . Intermolecular Forces: Proceedings of the Fourteenth Jerusalem Symposium on Quantum Chemistry and Biochemistry Held in Jerusalem, Israel, 13–16, 1981; Pullman, B. , Ed.; Springer: Netherlands, pp. 331–342.

Jorgensen W. L., Chandrasekhar J., Madura J. D., Impey R. W., Klein M. L.. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983;79(2):926–935. doi: 10.1063/1.445869. DOI

Abascal J. L. F., Vega C.. A general purpose model for the condensed phases of water: TIP4P/2005. J. Chem. Phys. 2005;123:234505. doi: 10.1063/1.2121687. PubMed DOI

Cruces Chamorro V., Jungwirth P., Martinez-Seara H.. Building Water Models Compatible with Charge Scaling Molecular Dynamics. J. Phys. Chem. Lett. 2024;15(10):2922–2928. doi: 10.1021/acs.jpclett.4c00344. PubMed DOI PMC

Zeron I. M., Abascal J. L. F., Vega C.. A force field of Li+, Na+, K+, Mg2+, Ca2+, Cl–, and in aqueous solution based on the TIP4P/2005 water model and scaled charges for the ions. J. Chem. Phys. 2019;151(13):134504. doi: 10.1063/1.5121392. PubMed DOI

Nencini R., Tempra C., Biriukov D., Riopedre-Fernandez M., Cruces Chamorro V., Polák J., Mason P. E., Ondo D., Heyda J., Ollila O. H. S., Jungwirth P.. et al. Effective Inclusion of Electronic Polarization Improves the Description of Electrostatic Interactions: The prosECCo75 Biomolecular Force Field. J. Chem. Theory Comput. 2024;20(17):7546–7559. doi: 10.1021/acs.jctc.4c00743. PubMed DOI PMC

Shanks B. L., Sullivan H. W., Shazed A. R., Hoepfner M. P.. Accelerated Bayesian Inference for Molecular Simulations using Local Gaussian Process Surrogate Models. J. Chem. Theory Comput. 2024;20(9):3798–3808. doi: 10.1021/acs.jctc.3c01358. PubMed DOI

Pluhařová E., Fischer H. E., Mason P. E., Jungwirth P.. Hydration of the chloride ion in concentrated aqueous solutions using neutron scattering and molecular dynamics. Mol. Phys. 2014;112(9–10):1230–1240. doi: 10.1080/00268976.2013.875231. DOI

Sindt J. O., Alexander A. J., Camp P. J.. Structure and Dynamics of Potassium Chloride in Aqueous Solution. J. Phys. Chem. B. 2014;118(31):9404–9413. doi: 10.1021/jp5049937. PubMed DOI

Badyal Y. S., Barnes A. C., Cuello G. J., Simonson J. M.. Understanding the Effects of Concentration on the Solvation Structure of Ca2+ in Aqueous Solution. II: Insights into Longer Range Order from Neutron Diffraction Isotope Substitution. J. Phys. Chem. A. 2004;108(52):11819–11827. doi: 10.1021/jp046476c. DOI

Kohagen M., Mason P. E., Jungwirth P.. Accounting for Electronic Polarization Effects in Aqueous Sodium Chloride via Molecular Dynamics Aided by Neutron Scattering. J. Phys. Chem. B. 2016;120(8):1454–1460. doi: 10.1021/acs.jpcb.5b05221. PubMed DOI

Mason P. E., Ansell S., Neilson G. W.. Neutron diffraction studies of electrolytes in null water: A direct determination of the first hydration zone of ions. J. Phys.: Condens. Matter. 2006;18:8437. doi: 10.1088/0953-8984/18/37/004. PubMed DOI

Abraham M. J., Murtola T., Schulz R., Páll S., Smith J. C., Hess B., Lindahl E.. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX. 2015;1-2:19–25. doi: 10.1016/j.softx.2015.06.001. DOI

Hoover W. G.. Canonical dynamics: Equilibrium phase-space distributions. Phys. Rev. A. 1985;31(3):1695–1697. doi: 10.1103/PhysRevA.31.1695. PubMed DOI

Parrinello M., Rahman A.. Polymorphic transitions in single crystals: A new molecular dynamics method. J. Appl. Phys. 1981;52(12):7182–7190. doi: 10.1063/1.328693. DOI

Essmann U., Perera L., Berkowitz M. L., Darden T., Lee H., Pedersen L. G.. A smooth particle mesh Ewald method. J. Chem. Phys. 1995;103(19):8577–8593. doi: 10.1063/1.470117. DOI

Hess B.. Determining the shear viscosity of model liquids from molecular dynamics simulations. J. Chem. Phys. 2002;116(1):209–217. doi: 10.1063/1.1421362. DOI

Maginn E. J., Messerly R. A., Carlson D. J., Roe D. R., Elliot J. R.. Best Practices for Computing Transport Properties 1. Self-Diffusivity and Viscosity from Equilibrium Molecular Dynamics Article v1.0. Living J. Comput. Mol. Sci. 2019;1(1):6324–6324. doi: 10.33011/livecoms.1.1.6324. DOI

Yeh I.-C., Hummer G.. System-Size Dependence of Diffusion Coefficients and Viscosities from Molecular Dynamics Simulations with Periodic Boundary Conditions. J. Phys. Chem. B. 2004;108(40):15873–15879. doi: 10.1021/jp0477147. DOI

Kostal V., Jungwirth P., Martinez-Seara H.. Nonaqueous Ion Pairing Exemplifies the Case for Including Electronic Polarization in Molecular Dynamics Simulations. J. Phys. Chem. Lett. 2023;14(39):8691–8696. doi: 10.1021/acs.jpclett.3c02231. PubMed DOI PMC

Hui C., de Vries R., Kopec W., de Groot B. L.. Effective polarization in potassium channel simulations: Ion conductance, occupancy, voltage response, and selectivity. Proc. Natl. Acad. Sci. U. S. A. 2025;122(21):e2423866122. doi: 10.1073/pnas.2423866122. PubMed DOI PMC

Dočkal J., Lísal M., Moučka F.. Polarizable force fields for accurate molecular simulations of aqueous solutions of electrolytes, crystalline salts, and solubility: Li+, Na+, K+, Rb+, F-, Cl-, Br-, I- J. Mol. Liq. 2022;362:119659. doi: 10.1016/j.molliq.2022.119659. DOI

Dočkal J., Mimrová P., Lísal M., Moučka F.. Structure of aqueous alkali metal halide electrolyte solutions from molecular simulations of phase-transferable polarizable models. J. Mol. Liq. 2024;394:123797. doi: 10.1016/j.molliq.2023.123797. DOI

Ikeda T., Boero M., Terakura K.. Hydration of alkali ions from first principles molecular dynamics revisited. J. Chem. Phys. 2007;126(3):034501. doi: 10.1063/1.2424710. PubMed DOI

Hofer T. S.. Solvation Structure and Ion-Solvent Hydrogen Bonding of Hydrated Fluoride, Chloride and Bromide-A Comparative QM/MM MD Simulation Study. Liquids. 2022;2(4):445–464. doi: 10.3390/liquids2040026. DOI

Tongraar A., Hannongbua S., Rode B. M.. QM/MM MD Simulations of Iodide Ion (I-) in Aqueous Solution: A Delicate Balance between Ion-Water and Water-Water H-Bond Interactions. J. Phys. Chem. A. 2010;114(12):4334–4339. doi: 10.1021/jp910435d. PubMed DOI

Azam S. S., Hofer T. S., Randolf B. R., Rode B. M.. Hydration of Sodium­(I) and Potassium­(I) Revisited: A Comparative QM/MM and QMCF MD Simulation Study of Weakly Hydrated Ions. J. Phys. Chem. A. 2009;113(9):1827–1834. doi: 10.1021/jp8093462. PubMed DOI

Guàrdia E., Skarmoutsos I., Masia M.. On Ion and Molecular Polarization of Halides in Water. J. Chem. Theory Comput. 2009;5:1449–1453. doi: 10.1021/ct900096n. PubMed DOI

Marcus Y.. Effect of Ions on the Structure of Water: Structure Making and Breaking. Chem. Rev. 2009;109(3):1346–1370. doi: 10.1021/cr8003828. PubMed DOI

Ohtaki H., Radnai T.. Structure and dynamics of hydrated ions. Chem. Rev. 1993;93(3):1157–1204. doi: 10.1021/cr00019a014. DOI

Ramos S., Barnes A. C., Neilson G. W., Capitan M. J.. Anomalous X-ray diffraction studies of hydration effects in concentrated aqueous electrolyte solutions. Chem. Phys. 2000;258(2–3):171–180. doi: 10.1016/S0301-0104(00)00132-4. DOI

Fulton J. L., Pfund D. M., Wallen S. L., Newville M., Stern E. A., Ma Y.. Rubidium ion hydration in ambient and supercritical water. J. Chem. Phys. 1996;105(6):2161–2166. doi: 10.1063/1.472089. DOI

Laliberté M., Cooper W. E.. Model for Calculating the Density of Aqueous Electrolyte Solutions. J. Chem. Eng. Data. 2004;49(5):1141–1151. doi: 10.1021/je0498659. DOI

Sedano L. F., Blazquez S., Noya E. G., Vega C., Troncoso J.. Maximum in density of electrolyte solutions: Learning about ion-water interactions and testing the Madrid-2019 force field. J. Chem. Phys. 2022;156:154502. doi: 10.1063/5.0087679. PubMed DOI

Gámez F., Sedano L. F., Blazquez S., Troncoso J., Vega C.. Building a Hofmeister-like series for the maximum in density temperature of aqueous electrolyte solutions. J. Mol. Liq. 2023;377:121433. doi: 10.1016/j.molliq.2023.121433. DOI

Blazquez S., Conde M. M., Vega C.. Scaled charges for ions: An improvement but not the final word for modeling electrolytes in water. J. Chem. Phys. 2023;158:054505. doi: 10.1063/5.0136498. PubMed DOI

Chattopadhyay A., Mandalaparthy V., van der Vegt N. F. A.. Determination of aqueous solubility of NaCl in molecular dynamics simulation using the Kirkwood-Buff method. J. Chem. Phys. 2025;162(17):174116. doi: 10.1063/5.0264104. PubMed DOI

Blazquez S., Conde M. M., Abascal J. L. F., Vega C.. The Madrid-2019 force field for electrolytes in water using TIP4P/2005 and scaled charges: Extension to the ions F-, Br-, I-, Rb+, and Cs. J. Chem. Phys. 2022;156:044505. doi: 10.1063/5.0077716. PubMed DOI