were achieved using Python. Plots were generated with Matplotlib 58,59 and structures were visualized using Vmd. A data set containing PDB files of the reactant and product starting structures, a modified AMBER95 force field file, AMS fragment files for the ligands and ions, and the AMS input files for all geometry optimizations and single point calculations is available at Ref. All QM calculations were performed using the GGA exchange-correlation functional PBE. In contrast to Ref. 15, we did not encounter a closing of the HUMO-LUMO gap with increasing size of the QM region. Instead, the HOMO-LUMO gap remained constant at about 1 eV for the larger QM regions (see Supporting Information, Fig. ). Note that the results presented in Ref. 15 that will be discussed in the following, have been obtained with the range-separated hybrid functional ωPBEh, which also avoids a spurious closing of the HOMO-LUMO gap.