Transition metals are often harder to treat computationally and results for organometallic systems typically have larger errors, so we expect that the difference in the DLPNO-CCSD(T) approaches will be stronger for the metalloenzymes than the organic enzymes, and indeed this is observed in the subset MMADs in figure . For each rung, the MMAD is much less sensitive to the choice of reference level of theory for the organic enzymes than the metalloenzymes, with the hybrid MMAD increasing by 0.4 kcal/mol with each step up in reference accuracy for the metalloenzymes, but less than 0.1 kcal/mol across all three levels for the organic enzymes. Subset MADs for all DFT-D3corrected functionals are shown in figure in the Supporting Information, and we note that some of the hybrid DFAs (such as CAM-B3LYP-D3(BJ), M062X-D3(0) and BHLYP-D3(BJ)) see differences in their MADs of around 1 kcal/mol between the two CPS-extrapolated levels of theory, while there are a few more observed rearrangements in the functional rankings as well. The behavior seen in the overall results, with the MADs of the hybrids increasing and double hybrids decreasing with the accuracy of the references, is not observed for the organic enzymes as it is mostly due to Hc RE2. As shown in figure 2, this RE gets more negative across our three reference levels of theory; as the deviations are calculated RE DF A -RE ref. , the lower references make the deviations more positive. This results in increased magnitudes for the hybrids, which already have positive deviations at the CPS(5,6) level, while the negative deviations of the double hybrids shift closer to zero.