The number-adaptive multiscale QM/MM molecular dynamics simulation: Application to liquid water

► Adaptive multiscale QM/MM-MD methods are a powerful tool for solution chemistry. ► Force smoothing is inevitable to treat solvent molecule exchange between QM and MM. ► A new smoothing method is proposed on the solvent molecule number-basis in T-region. ► In N-adaptive multiscale QM/MM-MD method, the total energy is conserved very well. ► Hydration structure is reproduced correctly by including some solvent molecules in QM.