To validate the new MiMiC-based QM/MM implementation, we performed simulations on four molecular systems of varying size and composition as described in the Computational Details (Sec. 4). Figure : Fluctuation of the total energy per particle with respect to time for QM/MM-MD simulations in the NVE ensemble of the Wat(aq) (top panel), Ace(aq) (middle panel), and BuOH(ace) (bottom panel) systems within the BO or CP approach using short-range (SR) coupling for the entire system or including long-range (LR) coupling with short-range cutoffs of 28, 30, and 32 a.u. for Wat(aq), Ace(aq), and BuOH(ace), respectively. The change in energy per particle is given relative to the average energy (∆E(t) = E(t) -E ).