NENCI-2021. 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 ∼8000 Non-Equilibirum Non-Covalent 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–π and anion–π complexes, a fundamentally important class of non-covalent interactions that are found throughout nature and pose a substantial challenge to theory, and (ii) systematically sampling all 141 intermolecular potential energy surfaces (PESs) 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× to 1.1× the equilibrium separation) and nine intermolecular angles per distance (five for each ion–π complex), yielding an extensive database of 7763 benchmark intermolecular interaction energies (Eint) obtained at the coupled-cluster with singles, doubles, and perturbative triples/complete basis set [CCSD(T)/CBS] level of theory. The Eint values in NENCI-2021 span a total of 225.3 kcal/mol, ranging from −38.5 to +186.8 kcal/mol, with a mean (median) Eint 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 symmetry-adapted perturbation theory (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 (3499), induction (700), dispersion (1372), or mixtures thereof (2192). A critical error analysis performed on a representative set of intermolecular complexes in NENCI-2021 demonstrates that the Eint values provided herein have an average error of ±0.1 kcal/mol, even for complexes with strongly repulsive Eint values, and maximum errors of ±0.2–0.3 kcal/mol (i.e., ∼±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 approximations, wavefunction theory methods, and machine learning based intra- and inter-molecular potentials.

Non-Covalent Interactions Atlas benchmark data sets 5: London dispersion in an extended chemical space

“…Recently, two other large databases of benchmark non-covalent interactions have been introduced by other authors. The NENCI-2021 data set 4 combines the 66 dimers from the S66 data set 5,6 with another 35 complexes of organic molecules with water 7 and 40 new ion-π complexes, sampling both dissociation curves (up to a very repulsive region) and angular displacements, which results in 7763 data points computed at a proper benchmark level. It is a well-rounded data set for e.g.…”

S66x8 noncovalent interactions revisited: new benchmark and performance of composite localized coupled-cluster methods

“…Hence, accurate wavefunction ab initio methods are often essential for obtaining highly precise NCI energies. Over the past few years, several datasets have been proposed 25–38 for intra- and intermolecular noncovalent interactions involving biologically important organic molecules of different sizes. The strong and weak NCIs in biomolecules are particularly interesting because they often play prominent roles in determining their favorable structures, specific binding sites, and dynamics.…”

An Imbalance in the Force: The Need for Standardized Benchmarks for Molecular Simulation

“… 35 Considered as a whole, the NCIA to date contains 2206 unique dimers with 5 or 10 points along dissociation curves ( Table 4 ). Of the interaction databases, both DES370K 198 and NENCI2021 191 cover all the target elements. The NCIA 192 also has a very broad coverage but does not yet feature complexes with inorganic ions.…”

“… 72 It uses the SAPT+/CBS method for the benchmark values, which in turn were tested on S66, where the FF delivered an error of 0.16 kcal/mol. 190 Recently, the S66 and S101 complexes have been included in the NENCI2021 data set, 191 which broadens the coverage of elements, includes charged complexes and also an extended mapping of the potential energy surface. The potential energy surface mapping of NENCI2021 focuses, in the fashion of S101, on repulsive regions, with intermolecular distances ranging from 70 to 110% of the equilibrium distance.…”