Benchmarking Density Functional Theory Methods for Metalloenzyme Reactions: The Introduction of the MME55 Set

We
present a new benchmark set of metalloenzyme model reaction
energies and barrier heights that we call MME55. The set contains
10 different enzymes, representing eight transition metals, both open
and closed shell systems, and system sizes of up to 116 atoms. We
use four DLPNO–CCSD­(T)-based approaches to
calculate reference values against which we then benchmark the performance
of a range of density functional approximations with and without dispersion
corrections. Dispersion corrections improve the results across the
board, and triple-ζ basis sets provide the best balance of efficiency
and accuracy. Jacob’s ladder is reproduced for the whole set
based on averaged mean absolute (percent) deviations, with the double
hybrids SOS0-PBE0-2-D3­(BJ) and revDOD-PBEP86-D4 standing out as the
most accurate methods for the MME55 set. The range-separated hybrids
ωB97M-V and ωB97X-V also perform well here and can be
recommended as a reliable compromise between accuracy and efficiency;
they have already been shown to be robust across many other types
of chemical problems, as well. Despite the popularity of B3LYP in
computational enzymology, it is not a strong performer on our benchmark
set, and we discourage its use for enzyme energetics.