However, we had to exclude ring size changes from the analysis as the hybrid topology approach did not support bond-breaking during the transformations. Initially, the same radial layout from Ries et al. was used to assess the performance of the mapping algorithms, later an MST approach was studied. For the radial network, all the mapping approaches successfully lead to the calculation of the necessary 13 edges to obtain the complete ranking of compounds. Comparing the generated free energies from the different starting points Kartograf, 2D Lomap, and 3D