Therefore, the development of quantum-chemical fragmentation schemes remains an im-portant research avenue (for recent efforts, see, e.g., Refs. . Such fragmentation schemes should be (a) versatile in both their applicability to complex chemical systems, including proteins, and in their compatibility with quantum-chemical methods for the fragment calculations, (b) only introduce a small error due to the fragmentation while maintaining a reasonable computational cost, and (c) ideally only use a small number of chemically meaningful fragments. In the past years, our research group has pursued two lines of research towards this goal.