Accurate description of molecular dipole surface with charge flux implemented for molecular mechanics

The molecular dipole moment is strongly coupled to molecular geometry among different phases, conformational states, intermolecular interaction energy, and vibrational spectroscopy. Our previous inclusion of geometry dependent charge flux into the atomic multipole-based polarizable AMOEBA+ force field has shown significant improvement of water properties from gaseous to condensed phases [C. Liu et al., J. Phys. Chem. Lett. 11(2), 419–426 (2020)]. In this work, the parameterization of the CF model for a broad range of organic and biomolecular fragments is presented. Atom types are automatically assigned by matching the predefined SMARTS patterns. Comparing to the current AMOEBA+ model without the CF component, it is shown that the AMOEBA+ (CF) model improves the description of molecular dipole moments for the molecules we studied over both equilibrium and distorted geometries. For the equilibrium-geometry structures, AMOEBA+ (CF) reduces the mean square error (MSE) from 6.806 × 10−1 (without CF) to 4.249 × 10−4 D2. For non-equilibrium structures, the MSE is reduced from 5.766 × 10−1 (without CF) to 2.237 × 10−3 D2. Finally, the transferability of the CF model and parameters were validated on two sets of molecules: one includes molecules in the training set but with different geometries, and the other one involves new molecules outside of the training set. A similar improvement on dipole surfaces was obtained on the validation sets. The CF algorithms and parameters derived in this work are general and can be implemented into any existing molecular mechanical force fields.