Assessing the validity of <scp>DLPNO‐CCSD</scp>(T) in the calculation of activation and reaction energies of ubiquitous enzymatic reactions
Pedro Paiva, Maria J. Ramos, Pedro Alexandrino Fernandes
Abstract
Abstract The domain‐based local pair natural orbital coupled‐cluster with single, double, and perturbative triples excitation (DLPNO‐CCSD(T)) method was employed to portray the activation and reaction energies of four ubiquitous enzymatic reactions, and its performance was confronted to CCSD(T)/complete basis set (CBS) to assess its accuracy and robustness in this specific field. The DLPNO‐CCSD(T) results were also confronted to those of a set of density functionals (DFs) to understand the benefit of implementing this technique in enzymatic quantum mechanics/molecular mechanics (QM/MM) calculations as a second QM component, which is often treated with DF theory (DFT). On average, the DLPNO‐CCSD(T)/aug‐cc‐pVTZ results were 0.51 kcal·mol −1 apart from the canonic CCSD(T)/CBS, without noticeable biases toward any of the reactions under study. All DFs fell short to the DLPNO‐CCSD(T), both in terms of accuracy and robustness, which suggests that this method is advantageous to characterize enzymatic reactions and that its use in QM/MM calculations, either alone or in conjugation with DFT, in a two‐region QM layer (DLPNO‐CCSD(T):DFT), should enhance the quality and faithfulness of the results.