Nevertheless, our results demonstrate that the analysis of the sensitivity with respect to the MM point charges is a good starting point for the investigation of uncertainties in QM/MM calculations. We are planning to extent this work in the future by considering not only selected distortions of the MM point charges, but performing a full sensitivity analysis that allows one to identify the collective point charge variations that have the largest influence on QM/MM reaction energies, following our earlier work on structural distortions in theoretical spectroscopy. While the reliability of considering only one global distortion of the MM point charges is limited, such a more comprehensive assessment of the sensitivity can be expected to overcome the limitations of our present approach.