NENCI-2021 Part I: A Large Benchmark Database of Non-Equilibrium Non-Covalent Interactions Emphasizing Close Intermolecular Contacts

Abstract

In this work, we present nenci-2021, a benchmark database of approximately 8, 000 non-equilibrium noncovalent interaction energies for a large and diverse selection of intermolecular complexes of biological and chemical relevance. To meet the growing demand for large and high-quality quantum mechanical data in the chemical sciences, nenci-2021 starts with the 101 molecular dimers in the widely used S66 and S101 databases, and extends the scope of these works by: (i ) including 40 cation-and anion-π complexes, a fundamentally important class of non-covalent interactions (NCIs) that are found throughout nature and pose a substantial challenge to theory, and (ii ) systematically sampling all 141 intermolecular potential energy surfaces (PES) by simultaneously varying the intermolecular distance and intermolecular angle in each dimer. Designed with an emphasis on close contacts, the complexes in nenci-2021 were generated by sampling seven intermolecular distances along each PES (ranging from 0.7 × −1.1× the equilibrium separation) as well as nine intermolecular angles per distance (five for each ion-π complex), yielding an extensive database of 7, 763 benchmark intermolecular interaction energies (E int ) obtained at the CCSD(T)/CBS level of theory. The E int values in nenci-2021 span a total of 225.3 kcal/mol, ranging from −38.5 kcal/mol to +186.8 kcal/mol, with a mean (median) E int value of −1.06 kcal/mol (−2.39 kcal/mol). In addition, a wide range of intermolecular atom-pair distances are also present in nenci-2021, where close intermolecular contacts involving atoms that are located within the so-called van der Waals envelope are prevalent-these interactions in particular pose an enormous challenge for molecular modeling and are observed in many important chemical and biological systems. A detailed SAPT-based energy decomposition analysis also confirms the diverse and comprehensive nature of the intermolecular binding motifs present in nenci-2021, which now includes a significant number of primarily induction-bound dimers (e.g., cation-π complexes). nenci-2021 thus spans all regions of the SAPT ternary diagram, thereby warranting a new four-category classification scheme that includes complexes primarily bound by electrostatics (3, 499), induction (700), dispersion (1, 372), or mixtures thereof (2, 192). A critical error analysis performed on a representative set of intermolecular complexes in nenci-2021 demonstrates that the E int values provided herein have an average error of ± 0.1 kcal/mol, even for complexes with strongly repulsive E int values, and maximum errors of ± 0.2−0.3 kcal/mol (i.e., approximately ± 1.0 kJ/mol) for the most challenging cases. For these reasons, we expect that nenci-2021 will play an important role in the testing, training, and development of next-generation classical and polarizable force fields, density functional theory (DFT) approximations, wavefunction theory (WFT) methods, as well as machine learning (ML) based intra-and inter-molecular potentials.