Kartograf's atom mapping algorithm is based on minimizing the spatial distance between the mapped atoms to identify the MCS (see section ). The initial assumption of the atom mapper is that the coordinate space of the end-state molecules has a high spatial overlap and is considered static for the mapping process. This high overlap can be assumed because the input to the free energy pipelines typically comes from e.g. docking procedures into the same coordinate space, a previous ligand alignment, or manual modeling.