Fragmenstein can work with covalent compounds. In order to work with covalent compounds, Fragmenstein treats the attachment atom (stored as a dummy atom) and defined atoms from the warhead differently, primarily by protecting these during merging. To test the impact of having a covalent attachment, the placement of a published compound with two stereoisomers was replicated. In this study, only one enantiomer reacted with the thiol of the catalytic cysteine in the protein (NUDT7). This compound is merger of two hits (NU181 and PCM0102716) which were used for placement with Fragmenstein. The RMSD between the placed model and the crystal structure of the merger is 0.28 Å, while the combined RMSD values of the model and the structure against the parent hits are 0.65 and 0.61 Å, indicating that the slight conformational change resulting from the constrained minimisation is also seen in the crystal structure. This placement (Figure ) operation also showcases a feature of Fragmenstein borne out of having to operate on multiple hits. Namely, that some superposed substituents in the hits may act as red herrings and are ignored, in this example the hydroxyl of one hit (NU181) is automatically ignored from the mapping as it would otherwise impede the mapping of the second hit (PCM0102716) which has a group occupying the same space. In this fragment screens, as is common, a racemic mix first soaked in the crystal (NU308) and was subsequently chirally separated into two stereoisomers (NU442 and NU443). Whereas one stereoisomer (NU443) was found covalently bound, the other (NU442) was found not reacted. Placing with Fragmenstein the latter stereoisomer as a covalent compound (Supplementary figure ), yielded a pose with a 10% worse binding ∆G (predicted by Rosetta ref2015 scorefunction without constraint weights) than the former and with a 0.9 Å shift in the sulfur atom of the connected cysteine relative to the position in the parent hit, indicating that the covalent bond is expected to be strained as is confirmed in the crystal structure wherein the presumably worse reaction barrier was not overcome.