To address the above problems, we developed Fragmenstein. The governing idea behind Fragmenstein is striving for fidelity to the position of the inspiring hits based upon the assumption that the derivative compounds bind in a very similar way. The crucial difference is that the conformers are generated by stitching together the atoms of the parent hits for both de novo generation (combination) and for docking-like approach (placement), and subsequently minimised in place. To achieve this several tactics are employed to overcome certain issues, such as mapping partial overlaps to multiple parent molecules, merging rings and correcting impossible topologies.