In our reference method (conf1), we employ CREST in combination with the density functional tight-binding method GFN1-xTB . Performing conformer searches for the 10 molecules of Fig. , we find that between 3 and 90 conformers are identified within the default energy window of 6 kcal/mol (260 meV) above the lowest energy one, underscoring the conformational flexibility of molecules in our dataset. For these conformer ensembles, we show the wide range of encountered λ DFT values in Fig 2b . Importantly, there is little variation between the values of λ DFT calculated for the lowest-energy conformers at the GFN1-xTB and DFT level, which suggests that GFN1-xTB conformers are a reliable proxy for the true first-principles ground state geometry. Unfortunately, performing the full conformer search at the GFN1-xTB level is computationally prohibitive for hundreds of thousands of molecules, however.