One piece at a time
Illustration by Dominic Doyle
In fragment-based drug design, a library of drug “fragments” (top panel) are screened to find fragments that bind to “subpockets” on a target protein’s binding surface (middle panel).
NMR spectroscopy or X-ray crystallography provides a 3-dimensional structure of the protein binding to the drug fragments, showing how the fragments fit into the protein’s binding pocket and how they might be linked together.
The fragments are then linked together and assembled into a larger molecule that better fills up the target protein’s binding pocket (bottom panel).