The structure-based drug design core performs lead discovery to aid in the development of new pharmaceutical compounds. Lead discovery typically begins with a target protein. Ideally, X-ray crystallography or NMR data is available for the target, but this is not an absolute requirement where homology modeling is possible. The target receptor is discussed with the client 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.

Computational docking is perfomed with the UCSF DOCK package and other software developed by us exclusively for drug discovery. The structure-based design core is affiliated with the UF High Perfomance Computing Center, and all lead discovery jobs are executed on the University supercomputing cluster. The computational power of the cluster allows us to screen databases ranging from hundreds of thousands to millions of small molecules rapidly and accurately.

Results are presented to the client as a list of the top several hundred small molecules determined 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.

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