Previously, we found that this can give an indication of the accuracy of the resulting charges and reaction energies . The sensitivity of the DHAP VDD charge strongly increases until region 4. This behavior has also be seen for COMT and is a result of the increase in charge distribution opportunities inside the QM region. Afterwards, a slightly decreasing trend in the sensitivity can be observed, which corresponds to the expected behavior. For the reaction energy sensitivity we observe an increase with the first two residues added (region 2) and a subsequent constant decrease. Although region 7 leads to a higher reaction energy compared to similar-sized-regions, its sensitivity fits into the decreasing behavior with larger QM regions, i.e., this outlier is not detected by the gPCVA.