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

Domain-based local pair natural orbital Coupled Cluster Singles Doubles with Per- turbative Triples [DLPNO-CCSD(T)] is regularly used to calculate reliable bench- mark 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 stan- dard TightPNO, and CPS(6,7), which sur- passes it—as benchmark values to test den- sity functional approximations (DFAs) on a small set of organic and transition-metal- dependent enzyme active site models. Be- tween the different reference levels of the- ory there are changes in the magnitudes of the absolute deviations for all function- als, but these are small and there is mini- mal impact on the relative rankings of the tested DFAs. The differences are more sig- nificant for the metalloenzymes than the organic enzymes, so we repeat the tests on our entire ENZYMES22 set of organic enzyme active site models [J. Phys. Chem. A 2019, 123, 7057.] to confirm that using the CPS extrapolations for the reference values has negligible impact on the bench- marking outcomes. This means we can particularly recommend CPS(5,6) as an al- ternative to standard TightPNO settings for calculating reference values, increasing the applicability of DLPNO-CCSD(T) in benchmarking reaction energies and bar- rier heights of larger models of organic en- zymes. The DLPNO-CCSD(T)/CPS(6,7) energies for ENZYMES22 are finally pre- sented as the updated reference values for the set, reflecting the recent improvements in the method.