To mimic a scenario where the NMR ensemble is unknown, initial conformers were created using ETKDG version 3 as implemented in the RDKit . For spiramycin, this simple procedure did not yield a conformer with the correct configuration of the conjugated double bonds. Therefore, we instead generated 500 conformers using ETKDG version 3, and selected the one with the lowest energy after energy optimization with the MMFF94 force field as implemented in the RDKit.