In Generators using 3D-LB parameters, Shape Similarity with respect to the reference molecule is computed after 3D alignment of the generated results with the reference molecule.
The user selects an anchor, a sub-unit of the reference molecule, which plays a crucial role in this alignment process: it acts as a point of reference. For this reason, the anchor needs to also be present in generated molecules!
If the generated molecules are not aligned correctly to the reference ligand, the first thing to check is: is my anchor part of my starting fragment, or product constraints, so that all generated molecules contain it too?