Toward more efficient density‐based adaptive QM/MM methods

Adaptive QM/MM (quantum mechanical/molecular mechanical) methods repartition molecules on‐the‐fly into the QM and MM regions based on a partitioning criterion. A density‐based partitioning scheme offers a unique way of carrying out QM and MM assignments on the presence/absence of (non) covalent interactions between non‐QM core molecules and the QM core. Here, we present two improvements to promote our density‐based adaptive partitioning strategy for adaptive QM/MM calculations. First, bond formation/breaking processes between non‐QM core molecules and the QM core are monitored using a density‐based descriptor, to define an adaptive QM core region on the fly. Second, the density‐based adaptive QM/MM partitioning scheme is made efficient enough for large systems by utilizating an adaptive search region and a Voronoi style‐partitioning scheme. The adaptive search region is used to preselect the subset of molecules that may interact strongly enough with the QM core region, and then a density‐based interaction calculation is only carried out on this subset. A Voronoi style‐partitioning scheme achieves an efficient assignment of the density‐based interactions. An efficient density‐based adaptive quantum mechanical/molecular mechanical scheme in a single‐step using a Voronoi partitioning scheme is presented. An adaptive search region lowers the computational time by reducing the size of the system included for interaction analysis. An adaptive QM core enables the system to adapt to the formation/breaking of both strong and weak interactions.