Docking is often employed to shortlist compounds, however it has the problem that the outputted conformer may not reflect the binding of the fragment hits that inspired them, even though fragment hits with a common substructure are most often found positioned in a very similar manner . Were a docked derivative candidate to interact differently than its parents, the validity of its score would be rightfully put to question by an experimentalist. Several decomposition studies address the SAR additivity/superadditivity of certain functional groups and how the binding mode is maintained crystallographically. Here, the inverse direction is taken and is found also to be consistent; in Figure it was shown that in the Covid-Moonshot dataset of the crystallised derivative compounds that bound similarly to their parent (69%), 82% are placed by Fragmenstein with an RMSD under 2 Å compared to 22% by pharmacophoreconstrained docking. Confirming the importance of obeying the position of the atoms in the parent hits. Fragmenstein has a very high success rate in combining parent hits and yields several virtual compounds in makeon-demand space (Table ). Fragmenstein aims to preserve the interactions of the parent hits unlike other methods. Nevertheless, in assessing the elaborations, one may be misled by the metrics used. Gibbs free energy of binding can be misleading, especially when constraints are involved: reducing the number of constraints improves this metric, whereas there are fewer interactions.