We consider the MM point charges q MM as one of the most important sources of uncertainty and want to systematically analyze the effect of variations in the MM point charges on our QoI, i.e., the reaction energy ∆E reaction QM/MM (q MM ). To this end, we follow our earlier work on the sensitivity of calculated spectra with respect to distortions of the molecular structure and consider a collective variation of the MM point charges, i.e.,