Additional Filters by Chemical Rules/Pre-Mapping In an effort to optimize atom mappings concerning the previously mentioned objectives, we offer users the ability to filter the resulting atom mappings using rule-based filters (see Figure ). Several filters have already been implemented, such as those that prevent element changes in the mapping, hydrogen atoms being mapped onto heavy atoms, and alterations in molecule flexibility for example by ring-breaking or molecule ring size changes. The latter can cause issues in many Figure : Kartografs' Atom Mapping Approach assumes as input a well-aligned pair of molecules A (dark blue) and B (beige). The approach calculates distances (red) between all atoms in both ligands. Subsequently, a distance pre-filter is applied, significantly reducing the search scope by allowing only reasonable atom mapping distances (default cut-off 0.95 Å ). Optionally, users can mask atoms to narrow down the search space. An initial optimal mapping (green) is determined based on distances using the Kuhn-Munkres algorithm. Additionally, users can apply filter rules to the initial mapping, such as restricting hydrogento-heavy atom mapping and preventing ring breaks. From the resulting mapping, the largest connected set is returned as the mapped core region of the hybrid topology approach. singularities during the simulations. One solution to this problem was introduced by Wang et al., who proposed softbond bonded potentials that enable scaffold hops in core regions. Alternatively, such mappings can simply be avoided, if a hybrid topology core region remains. Furthermore, users have the option to provide pre-mappings, allowing for the iterative generation of the mappings or ensuring the mapping of specific sub-structures (see Figure ).