Exploring CPS-Extrapolated DLPNO–CCSD(T₁) Reference Values for Benchmarking DFT Methods on Enzymatically Catalyzed Reactions

Abstract

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 computational cost significantly lower than that of 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 Goerigk, L. J. Phys. Chem. A 2019, 123, 7057−7074] to confirm that using the CPS extrapolations for the reference values has negligible impact on the benchmarking outcomes. This means that we can particularly recommend CPS(5,6) as an alternative to standard TightPNO settings for calculating reference values, increasing the applicability of DLPNO−CCSD(T) in benchmarking reaction energies and barrier heights of larger models of organic enzymes. DLPNO−CCSD(T 1 )/CPS(6,7) energies for ENZYMES22 are finally presented as updated reference values for the set, reflecting the recent improvements in the method.

Encapsulation of charged halogens by the 512 water cage

“…35–37 The TightPNO settings have been suggested for accurately predicting the binding energies of non-covalently bonded clusters. 38–40 In addition to the “semi-canonical” perturbative triples correction approximation DLPNO-CCSD(T), we also tested (i) the improved iterative triples correction DLPNO-CCSD(T1) 41,42 and (ii) an extrapolation 43–48 of DLPNO-CCSD(T) to CBS via the Ahlrichs def2-TZVPP/def2-QZVPP basis sets. 49,50 All calculations were done with the default grids and tight self-consistent-field (SCF) convergence thresholds.…”

Eliminating Imaginary Vibrational Frequencies in Quantum-Chemical Cluster Models of Enzymatic Active Sites

“…An alternative to QM/MM simulations for mechanistic studies of enzyme catalysis is to use limited “cluster” models of the active site. − This approach neglects any atomistic description of the larger protein environment, and is thus unable to describe chemical transformations that are driven by conformational changes of the protein, but for a limited set of problems the QM-cluster approach has an important advantage of simplicity. By eliminating the need for MD sampling (requiring a QM energy and gradient evaluation every 1–2 fs), the cluster approach becomes amenable to higher-level electronic structure calculations. , …”