Mitigating Freezing Artifacts in Polar Coarse-Grained Water through Rebalancing Electrostatic and van der Waals Interactions: A Case Study of the pSPICA Force Field

Abstract Coarse-grained (CG) water models with explicit electrostatic interactions are essential for capturing the dielectric response of biomolecular systems. However, many CG water models exhibit pronounced freezing artifacts under ambient conditions. Using the SPICA force-field family as a case study, we examined the influences of charge topology, background dielectric screening (εbg), and Lennard–Jones (LJ) interaction strength on the freezing tendency of CG water. Among the models examined here, which all reproduce the target density and surface tension at 298 K, changing the charge topology from a linear dipole to V-shaped geometries did not substantially lower the melting temperature (Tm). Instead, Tm was more sensitive to the LJ interaction strength. Reducing εbg strengthens the electrostatic contribution, allowing the LJ attraction to be weakened while maintaining the target properties. On this basis, we propose a parametrization framework for introducing a permanent dipole into a nonpolar CG water model while mitigating its freezing tendency. Using this framework, we developed pSPICA2, which reduces Tm from 384 to 302 K while retaining accurate density, surface tension, and dielectric response at 298 K. Although Tm remains above the experimental value of 273 K in this work, the proposed framework offers a practical route for developing polar CG water models with reduced freezing artifacts.