[1] It is based on identifying small chemical fragments, which may bind only weakly to the biological target, and then growing them or combining them to produce a lead with a higher affinity.
In HTS, libraries with up to millions of compounds, with molecular weights of around 500 Da, are screened, and nanomolar binding affinities are sought.
In contrast, in the early phase of FBLD, libraries with a few thousand compounds with molecular weights of around 200 Da may be screened, and millimolar affinities can be considered useful.
In fragment-based drug discovery, the low binding affinities of the fragments pose significant challenges for screening.
At modern X-ray crystallography synchrotron beamlines, several hundred data sets of protein-ligand complex crystal structures can be obtained within 24 hours.