Perhaps the constraints of the search algorithm will define the mechanism of query. Once identified, substructures must be manipulated in ways that benefit the user. This is more vague than the first demand, but perhaps the computational implications can be best illustrated with a concrete example. It would be nice to look at them. But coordinates from the PDB are scattered all over 3D space.
Superposition requires two sets a coordinates.
Surely not all fifty of our hits have the same amino acid sequence. They can't be expected to have the same atoms. If we are interpreting electron density, it would be nice to have the substructures overlaid on the density. Fifty substructures is a lot to look at. It would be nice to pick one and include it in our model, but there are the amino acid sequence differences to contend with.