Transferability of ion force fields to OPC water: Maintaining single-ion and ion-pairing properties

Abstract

Accurate ion force fields are essential for molecular dynamics simulations of biomolecular systems, particularly in combination with modern water models such as OPC. While OPC water provides an accurate description of key water properties and has been successfully applied in biomolecular simulations, the transferability of existing ion force fields to this model remains an open question. Here, we systematically assess the transferability of monovalent and divalent ion force field parameters (Li+, Na+, K+, Cs+, Mg2+, Ca2+, Sr2+, Ba2+, Cl-, and Br-) to OPC water by comparing single-ion and ion-pairing properties with experimental data. Our analysis reveals that no single literature parameter set provides accurate results for all ions when directly transferred to OPC water. We hence introduce the MS/G-LB(OPC) force field, which combines Mamatkulov-Schwierz-Grotz cation parameters with Loche-Bonthuis anion parameters. MS/G-LB(OPC) reproduces hydration free energies, first-shell structural properties, and activity derivatives at low salt concentrations. Our results demonstrate that transferring ion parameters to OPC can lead to significant and ion-specific deviations from experimental data, making careful validation essential. At the same time, the systematic transfer and combination of ion parameters from existing force fields can provide a practical and computationally efficient alternative to full reparameterization. MS/G-LB(OPC) is available at https://git.rz.uni-augsburg.de/cbio-gitpub/opc-ion-force-fields.