Treating Polarization Effects in Charged and Polar Bio-Molecules Through Variable Electrostatic Parameters.

Abstract

Polarization plays important roles in charged and hydrogen bonding containing systems. Much effort ranging from the construction of physics-based models to quantum mechanism (QM)-based and machine learning (ML)-assisted models have been devoted to incorporating the polarization effect into the conventional force fields at different levels, such as atomic and coarse grained (CG). The application of polarizable force fields or polarization models was limited by two aspects, namely, computational cost and transferability. Different from physics-based models, no predetermining parameters were required in the QM-based approaches. Taking advantage of both the accuracy of QM calculations and efficiency of molecular mechanism (MM) and ML, polarization effects could be treated more efficiently while maintaining the QM accuracy. The computational cost could be reduced with variable electrostatic parameters, such as the charge, dipole, and electronic dielectric constant with the help of linear scaling fragmentation-based QM calculations and ML models. Polarization and entropy effects on the prediction of partition coefficient of druglike molecules are demonstrated by using both explicit or implicit all-atom molecular dynamics simulations and machine learning-assisted models. Directions and challenges for future development are also envisioned.