Exploring CPS-extrapolated DLPNO-CCSD(T1) reference values for benchmarking DFT on enzymatically catalyzed reactions

Domain-based local pair natural orbital Coupled Cluster Singles Doubles with Perturbative Triples [DLPNO-CCSD(T)] is regularly used to calculate reliable benchmark reference values at a significantly lower computational cost compared to canonical CCSD(T). Recent work has shown that even greater accuracy can be obtained at only a small additional cost through extrapolation to the complete PNO space (CPS) limit. Herein we test two levels of CPS extrapolation—CPS(5,6), which approximates the accuracy of standard TightPNO, and CPS(6,7),which surpasses it—as benchmark values to test density functional approximations (DFAs) on a small set of organic and transition-metal-dependent enzyme active site models. Between the different reference levels of theory there are changes in the magnitudes of the absolute deviations for all functionals, but these are small and there is minimal impact on the relative rankings of the tested DFAs. The differences are more significant for the metalloenzymes than the organic enzymes, so we repeat the tests on our entire ENZYMES22 set of organic enzyme active site models to confirm that using the CPS extrapolations for the reference values has negligible impact on the benchmarking outcomes. This means we can particularly recommend CPS(5,6) as an alternative to standard TightPNO settings to increase the applicability of DLPNOCCSD(T) in calculating accurate BHs and REs for larger models of organic enzymes. The DLPNO-CCSD(T)/CPS(6,7) energies for ENZYMES22 are finally presented as the updated reference values for the set, reflecting the recent improvements in the method.