In order to obtain representative libraries of carboxylic acids and amines, the Reaxys database 34 was queried to identify commercially available carboxylic acids, primary alkyl amines, and secondary alkyl amines that would be applicable to amide coupling reactions (Figure ). To ensure broad representation of molecules relevant to medicinal chemistry for downstream library applications, external validation sets of acids and amines were also compiled from Enamine's building block sets 36 and from acid and amine fragments of existing amide-containing drugs mined from the Broad Institutes Drug Repurposing Hub. The full lists of compounds are available on Figshare. Previous studies have revealed the utility of molecular descriptors that encompass the dynamic range of conformers that a molecule can adopt within a given energetic window. To this end, we conducted automated conformational searching and clustering with Schrodinger's Maestro 39 to access representative conformational ensembles for each compound, which were then further optimized using the Gaussian 16 software at the M06-2X/def2-TZVP-SDD(I, Sn, Se)// B3LYP-D3(BJ)/6-31G(d,p)-LANL2DZ(I, Sn, Se) level of theory. Natural bond orbitals (NBO) and spectroscopic parameters were further evaluated at the DFT level of theory on these optimized geometries. To process these calculations, a Get Properties jupyter notebook was developed to enable the collection of descriptors at the molecule-level, in addition to atom-and bond-level properties for a conserved moiety of interest. Specifically, for each of these three libraries, we collected global properties (e.g., frontier molecular orbital energies of the HOMO and LUMO, polarizability, dipole moment, solvent accessible surface area, and solvent accessible volume) of the molecule, and tabulated the atom-level properties (e.g., NBO natural population analysis partial charge, NMR chemical shift, and buried volume) of conserved atoms (Figure ). In the case of the amine libraries, additional atom-level properties relevant to the nitrogen of the amine (i.e., pyramidalization, lone pair energy, and lone pair occupancy) were also collected. Bond-level Sterimol values were calculated for both the acid and the primary amine moieties to give insight into the steric environment of their substituents. Additionally, for the acid library, the IR harmonic stretching frequency of the carbonyl was compiled.