To quantitatively assess the quality of the ensemble when minimized with OpenFF 2.0.0 and the GNNIS model, we calculated balanced accuracies for ensembles minimized using OpenFF 2.0.0 with (i) no solvent (in vacuum), (ii) the GB-Neck2 implicit solvent model, and (iii) the GNNIS model, and for ensembles simulated with the same force field in explicit solvent. The balanced accuracy indicates whether low-lying minima (i.e., minima with free energies below one k B T) are correctly identified in an ensemble. An explanatory illustration is provided in SI Figure ). The correct prediction of low-energy conformers is especially important as they contribute significantly to experimental observables, e.g., NMR or IR spectra. As shown in Figure , the GNNIS minimization detects low-lying free-energy minima with high precision, significantly outperforming GB-Neck2. In the case of set P, the minimization procedure with the GNNIS model even approaches the balanced accuracy obtained with explicit-solvent simulations evaluated using standard sampling times (i.e., 50 ns and 100 ns REST2 simulations for set C and P, respectively). As the compounds of set P are larger and more flexible compared to those in set C, longer sampling times would be required in explicit simulations to further increase the achievable balanced accuracy.