To determine the optimal treatment of the electrostatic QM/MM interactions during the dynamics, we tested various short-range cutoff distances and multiple orders. Figs. 4a and 4b illustrate the total energy and maximum force, respectively, for each combination of short-range cutoff and multipole expansion order, using a fully short-range calculation as the reference. From these results, we observe convergence in the maximum force with a shortrange cutoff of 65 Å and a multiple expansion of 8. Additionally, we evaluated the convergence of the plane wave cutoff energy by testing values from 50 Ry to 110 Ry in increments of 5 Ry. The total energy and maximum force were compared to those obtained with a large reference cutoff of 120 Ry (Fig. and). Based on these results, we selected a plane wave cutoff of 100 Ry, corresponding to a real-space DFT grid of 600 × 400 × 400. Fig. presents the time-evolution of energy and temperature during a 50 ps QM/MM MD simulation. The total energy, which includes the Kohn-Sham energy and the kinetic energy of all atoms, is shown in Fig. . Fig. shows the Kohn-Sham energy of the QM region, while Fig. presents the temperature evolution of the QM and MM regions.