We also examined the robustness of the QM/MM implementation by monitoring the energy fluctuations of the Wat(aq), Ace(aq), and BuOH(ace) systems during QM/MM-MD simulations in the NVE ensemble. Simulations using BO and CP methods were performed both with and without long-range coupling. For the simulations of Wat(aq) and Ace(aq) that include the long-range coupling, we first performed additional equilibrations for ∼2.42 ps (5,000 steps) including the long-range coupling and otherwise using the same settings as described above. Short-range cutoffs of 28, 30, and 32 a.u. were used for Wat(aq), Ace(aq), and BuOH(ace), respectively, while in the simulations without long-range coupling the shortrange coupling was used for the entire system. The same settings as described above were used for the QM/MM-BOMD simulations except that the convergence threshold was set to 1.0 • 10 -6 a.u. and eight previous steps were used in the wavefunction extrapolation. For the QM/MM-CPMD simulations, a time step of ∼0.07 fs (3.0 a.u.) was used for Wat(aq) and ∼0.12 fs (5.0 a.u.) for the other two systems. The fictitious electron mass was set to 700 a.u. for all systems except for Wat(aq) where it was set to 800 a.u.