Adaptive-Partitioning Multilayer Dynamics Simulations: 1. On-the-Fly Switch between Two Quantum Levels of Theory.

We propose to generalize the previously developed two-layer permuted adaptive-partitioning quantum-mechanics/molecular-mechanics (QM/MM), which reclassifies atoms as QM or MM on-the-fly in dynamics simulations, to multilayer adaptive-partitioning algorithms that enable multiple levels of theory. In this work, we formulate two new algorithms that smoothly interpolate the energy between two QM (Q1 and Q2) levels of theory. The first "permuted adaptive-partitioning" scheme is based on the weighted many-body expansion of the potential, as in the adaptive-partitioning QM/MM. Unconventional and potentially more efficient, the second "interpolated adaptive-partitioning" method employs alchemical QM calculations with Q1/Q2-mixed basis sets, Fock matrices, and overlap matrices. To our knowledge, this is the first time that such alchemical calculations are performed in QM, although they are routinely done in MM. Test calculations on water-cluster models show that both new algorithms indeed yield smooth energy curves when water molecules shift between Q1 and Q2.