In a first step, we reproduced the reaction energy convergence for the distance-based case similar to Ref. . Here, we defined the base pair G7-C14 as the minimal QM region 1 and consequently added the adjacent pair A6-T15 for region 2, then pair A8-T13, and so on. An overview of the different regions is given in Table . In Fig. , the dark blue graph represents the reaction energy with increasing QM region size for the distancebased inclusion of base pairs. The energy drastically decreases with 2 and 3 bp in the QM region, respectively, and converges at about 27.4 kcal/mol starting from 5 bp, which overall corresponds to the results in Ref. .