Electronic polarization is a property of ionic species that must be accurately captured to ensure reliable predictions in biomolecular simulations. Many biological processes, such as ligand-enzyme binding, membrane transport, and the regulation of DNA expression, depend on interactions between ions and molecules that are poorly described if polarization effects are neglected. Within a classical molecular dynamics paradigm, not accounting for polarization effects can lead to significant ion overbinding, leading to unrealistic predictions of free energy surfaces that often contradict experimental data. From a modeling perspective, these effects can be incorporated explicitly using models like Drude oscillators, or implicitly through mean-field approximations such as the electronic continuum correction (ECC). The ECC framework mimics charge screening by scaling charges according to the inverse square root of the solvent dielectric constant, adding no additional computational cost. In this study, we demonstrate that using neutron scattering data as a target for fitting force field parameters within an ECC framework yields remarkable agreement between empirical atomic size parameters and theoretical models of electronic polarization. Notably, we observe a systematic transition in the atomic size behavior from quantum to classical as charge density increases, a result that is not observed in other state-of-the-art biomolecular force fields. These findings highlight how structural data can impose physically meaningful constraints on force field development, resulting in models that align closely with theoretical descriptions of interatomic forces while implicitly addressing electronic polarization.
