Lead Discovery

The structure-based drug design core performs lead discovery to aid in the development of new pharmaceutical compounds. Lead discovery typically begins with a biomedically relevant target protein. Ideally, X-Ray Crystallography or NMR data is available for the target protein, but this is not an absolute requirement where homology modeling is possible. The target receptor is discussed with the investigators to identify active sites or particular pockets known to be involved in protein function. The target protein is computationally analyzed and a three-dimensional complement of each target site is described and refined.

Above: A successful compound docked into a pocket of Focal Adhesion Kinase.

Docking Process

Computational docking is performed with the UCSF DOCK package and other software developed here at the UF Health Cancer Center’s Structure-Based Drug Design Core exclusively for drug discovery research. The Structure-Based Drug Design Lab is affiliated with the UF High Performance Computing Center, and all lead discovery jobs are executed on the University supercomputing cluster. The computational power of the cluster allows us to screen chemical libraries ranging in size from hundreds of thousands to millions of small molecules rapidly, accurately and economically.


Results are presented to investigators as a list of the top several hundred small molecules estimated to have the highest binding affinity for the target site. Each targeted compound can be viewed in its predicted orientation in the target site, and all necessary information for compound ordering is provided. We routinely obtain the top 40 scoring compounds from the National Cancer Institutes Developmental Therapeutics Program for functional in vitro and in vivo testing.

To make a lead discovery request please visit our Docking Request page.