Quantitative Analysis of QM/MM Boundary Artifacts and Correction in Adaptive QM/MM Simulations

A quantum chemical treatment of solvation effects using the standard quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations is challenging due to QM and MM solvent exchange near the QM solute. To this end, various adaptive QM/MM methods have been proposed; free solvent exchanges are allowed via flexible switching of their identities between QM and MM systems depending on their distances from the QM solute. However, temporal and spatial discontinuities remain in the standard implementations of adaptive QM/MM approaches and continue to hamper stable and accurate dynamics simulations. We previously demonstrated that the size-consistent multipartitioning (SCMP) method achieves temporal continuity while, to some extent, avoiding spatial discontinuities. In the present study, we demonstrate that residual spatial discontinuities may lead to severe artifacts under certain conditions. Through quantitative analyses, we show that all multiscale including QM/MM methods might experience these problems, which so far have not been investigated in depth. To alleviate these artifacts, we propose a correction scheme in the framework of the SCMP approach and demonstrate its effectiveness using bulk water simulations.