| A continuum polarizable model was developed to treat electronic polarization. A dielectric constant of 3.3 with the van der Waals surface was found to best reproduce quantum mechanics dimer interaction energies of near 1,000 dimers of different types of interactions, covering pairwise interactions among protein main chains, side chains, and nucleic acid bases. Notably, the continuum polarizable model and parameters also showed satisfactory results for charged dimers, which were ruled out in previous studies. Furthermore, we tested the consistency of molecular mechanics dipole moments by both explicit and implicit dipole models with respect to the benchmark quantum mechanics method, and found neither strategies were satisfactory even if their interaction energies were well reproduced. Finally, we validated the compatibility of the continuum polarizable model to the optimized Van der Waals parameters designed for the latest general polarizable force field and found that the optimized VdW parameters showed better compatibility to the traditional ones. The continuum polarizable model shows potential in representing polarization effect at a higher efficiency compared to the explicit model. A heterogeneous dielectric scheme will be explored that specifically addresses the different chemical functional groups and assess its performance in more diversified chemical environments as needed in the drug discovery effort in future work. |
