For the calculation of the mean unsigned difference (MUD) values between conformer generation algorithm predicted structure and QM optimized structure, we used the energy values of structures with minimum RMSD to QM optimized structure even if the algorithm may find lower energy structures. This is because our reference points are QM optimized model and ideal structures, and we have not thoroughly explored all the conformers with QM calculations due to computational cost. The MUD values of DeepConf in predicting both QM optimized model and ideal structures (i.e., 〈∆𝐸 𝑚𝑜𝑑𝑒𝑙 𝑀𝐿-𝑄𝑀 〉 and 〈∆𝐸 𝑖𝑑𝑒𝑎𝑙 𝑀𝐿-𝑄𝑀 〉), are 3.62 and 3.12 kcal/mol, respectively, with a span from -21 kcal/mol to 24 kcal/mol for the model structures, and in a range of -8 to 14 kcal/mol on ideal structures. Similarly, the MUD value of ideal structures in Auto3D is 3.64 kcal/mol ranging between -8 kcal/mol to 17 kcal/mol. However, the MUD values of Auto3D predicted model structures deviate from the QM optimized model structures by 4.47 kcal/mol in a range of -23 kcal/mol and 24 kcal/mol, indicating slightly less confidence. Unfortunately, RDKit predictions using either MMFF94 or UFF do not give absolute energy values, so we could not directly compare RDKit predicted absolute energies to QM optimized energies. We also considered how the conformer generation algorithms perform predicting the energy gap between the two minima (QM optimized model and ideal) since this gap is related to the relative populations (Table and Figure ).