Automated Refinement of Property-Specific Polarizable Gaussian Multipole Water Models Using Bayesian Black-Box Optimization

The critical importance of water in sustaining life highlights the need for accurate water models in computer simulations, aiming to mimic biochemical processes experimentally. The polarizable Gaussian multipole (pGM) model, recently introduced for biomolecular simulations, improves the handling of complex biomolecular interactions. As an integral part of our initial exploration, we examined a minimalist fixed geometry three-center pGM water model using <i>ab initio</i> quantum mechanical calculations of water oligomers. However, our final model development was based on liquid-phase water properties, leveraging automated machine learning (AutoML) techniques for optimization. This allows the development of a framework to refine both van der Waals and electrostatic parameters of the pGM model, aiming to accurately reproduce specific properties such as the oxygen-oxygen radial distribution function, density, and dipole moment, all at 298 K and 1.0 bar pressure. The efficacy of the optimized three-center pGM water model, pGM3P-25, was assessed through simulations of a water box of 512 water molecules, showcasing marked enhancements in both accuracy and practical utility. Notably, the model accurately reproduces thermodynamic properties not explicitly included in training while significantly reducing the time and human effort required for optimization. It was found that pGM3P-25 can reproduce temperature-dependent properties such as density, self-diffusion constants, heat capacity, second virial coefficient, and dielectric constant, which are important in biomolecular simulations. This study underscores the potential of AutoML-driven frameworks to streamline parameter refinement for molecular dynamics simulations, paving the way for broader applications in computational chemistry and beyond.