All methods listed in table were applied in ORCA v5.0.2 with the def2-QZVPP basis set, except for the composite DFT (-3c) methods which used their own specific basis sets. Additional calculations with B3LYP, M06, PWPB95 and ωB2PLYP were done with the def2-SVP and def2-TZVPP basis sets. The ORCA implementation of the LibXC density functional library 155 was used to run MN15-L, MN15 and MPW1B95 calculations. DOD-SCAN, revDSD-PBEP86 and revDOD-PBEP86 were run in both the DFT-D3(BJ) and DFT-D4 115,156 parameterized forms. For B97M-V, ωB97M-V and ωB97X-V, the non-local VV10 kernel was used in its post-SCF implementation, as this strategy does not impact the results but can lead to a considerable speedup in calculations. The DFT-D3(BJ) dispersion correction with Becke-Johnson damping was used preferentially to the older, zero-damping DFT-D3(0) variant for all functionals except M06-L, MN15-L, M06 and M062X-the Minnesota functionals are parameterized to have better descriptions of mid-range interactions, but this leads to some double-counting effects when the D3(BJ) correction is applied. Specific dispersion correction damping parameters for B3LYP* have not been determined yet, so we follow the common approach of applying the standard B3LYP The DFT-D3(BJ)/4 dispersion correction replaces the VV10 kernel in this van-der-Waals functional, while its semi-local exchange-correlation component stays the same. b DFT-D3(0) correction. c Damping parameters for B3LYP* have yet to be defined, so we use the standard B3LYP damping parameters. d Range-separated functionals with variable amounts of Fock exchange. e The underlying parameters for these functionals differ between their D3(BJ) and D4 versions. f Scale factors for the same spin and opposite spin contributions to the MP2 correlation energy, respectively. damping parameters. and this is likely even more inappropriate in metalloenzymes where the coordination environments of the metal ions also need to be represented. We thus searched the literature for DFT and QM/MM studies of enzyme mechanisms, focusing on ones where the active site model or QM region contained up to 120 atoms and no more than 2 metal centers, so that the entire model could be used without needing to be simplified. The selected enzyme models, which range in size from 51-116 atoms and cover eight different transition metals, are: