Accurate Quantum Mechanics/Molecular Mechanics Simulation of Aqueous Solutions with Tailored Molecular Mechanics Models.

In recent years, quantum mechanical/molecular mechanical (QM/MM) methods have emerged that are designed specifically for chemical reactions in water. Despite the many advances, a remaining problem is that the patchwork of QM and MM descriptions changes the solvent structure. In a solvent as intricately connected as water, such structural changes can alter a chemical process even across large distances. Examples of structural artifacts in QM/MM water include density accumulation at the QM/MM boundary, decreased order, and density differences between regions. These issues are mostly apparent if the difference between the QM and the MM model is very large, which is often the case with water models. Here, we assess the QM/MM performance of simple MM models that are specifically parametrized to match selected data from a QM simulation of bulk water. To this end, we introduce a novel MM model (PM6-(DH+)-EFF) that reproduces PM6-DH+ water properties. We also assess a recent PBE-DFT-based MM model (PBE-EFF) that reproduces structural properties of bulk water simulated with PBE-DFT. Both models consist solely of tabulated potential energy terms for interactions between atom pairs. We compare the matched QM/MM results (PBE-DFT/PBE-EFF and PM6-DH+/PM6(-DH+)-EFF) with those from mismatched QM/MM simulations (PM6-DH+/PBE-EFF). The mismatched simulations reflect issues similar to those reported for other mismatched QM/MM pairs. The matched simulations yield very good results with water structures that barely deviate from the QM reference. In view of these findings, we strongly recommend adoption of specifically parametrized MM models in the QM/MM simulation of chemical processes in water.