Significant deviations from the unvaried curve are visible for ∆q = ±0.005. Overall, the variations do not affect the charge convergence behavior, but lead to different ligand-dependent observations concerning the sensitivity. For CAT and Mg 2+ , the VDD charge sensitivity decreases with increasing QM region size (with the exception of region 1 for CAT) and converges for region 4 and larger. For the largest QM regions 8 and 9, the sensitivity of the Mg 2+ charge is reduced to almost zero.