Harnessing Deep Learning for Optimization of Lennard-Jones Parameters for the Polarizable Classical Drude Oscillator...

The outcomes of computational chemistry and biology research, including drug design, are significantly influenced by the underlying force field (FF) used in molecular simulations. While improved FF accuracy may be achieved via inclusion of explicit treatment of electronic polarization, such an extension must be accompanied by optimization of van der Waals (vdW) interactions, in the context of the Lennard-Jones (LJ) formalism in the present study. This is particularly challenging due to the extensive nature of chemical space combined with the correlated nature of LJ parameters. To address this challenge, a deep learning (DL)-based parametrization framework is developed, allowing for sampling of wide ranges of LJ parameters targeting experimental condensed phase thermodynamic properties. The present work utilizes this framework to develop the LJ parameters for atoms associated with four distinct groups covering 10 different atom types. Final parameter selection was facilitated by quantum mechanical data on rare-gas interactions with the training set molecules. The chosen parameters were then validated through experimental hydration free energies and condensed phase thermodynamic properties of validation set molecules to confirm transferability. The ultimate outcome of utilizing this framework is a set of LJ parameters in the context of the polarizable Drude FF, which demonstrated improvement in the reproduction of both experimental pure solvent and crystal properties and hydration free energies of the molecules compared to the additive CHARMM General FF (CGenFF) including the ability of the Drude FF to accurately reproduce both experimental pure solvent properties and hydration free energies. The study also shows how correlations between difference in the reproduction of condensed phase data between model compounds may be used to direct the selection of new atom types and training set molecules during FF development.