The energy of all conformers in each generated ensemble was evaluated through density functional theory (DFT) calculations to avoid inaccuracies of the classical force fields employed by the different algorithms. This metric aimed to identify the algorithms capable of producing lower energy structures, serving as an indicator of the geometric correctness of the generated molecules. However, this metric should be interpreted cautiously, as experimental structures bound to proteins may exhibit internal energy strain, and although such structures reflect the free energy minimum, those states do not necessarily coincide with the structure of minimum potential energy . Nevertheless, excessively high energies could indicate problematic geometries, as previously observed for algorithms such as Balloon, RDKit, Frog2, ConfGen, cxcalc, and MOE . Lower energy states suggest sufficiently optimized geometries suitable for subsequent, more precise calculations of molecular properties. The energy distributions are shown in Figure . The average of the normalized energy (with respect to the lowest-energy state) is indicative of the energy window in a conformer ensemble. Moltiverse demonstrates the lowest global mean normalized energy value (37.79 kcal/mol) among all evaluated algorithms. This superior result can be attributed to Moltiverse's protocol, which incorporates a conformer refinement step using the semi-empirical GFN2-xTB method that ensures geometric correctness.