My research is focused on computer aided drug design. An area of specific interest to our lab is the design of enzymes essential for the biosynthesis of polyamines, which are critical for the replication of DNA and are elevated in a number of human tumors. This work has focused on the design of S-adenosylmethionin decarboxylase inhibitors as potential anti-cancer agents.
Through collaboration with other investigators at Moffitt, we have been involved in the computational design of inhibitors of other enzymes and inhibitors of protein-protein interactions that have therapeutic releveance in cancer. This work includes the following biomolecular targets: farnesyl transferase and geranylgeranyl transferase (in collaboration with Drs. Said Sebti and Nick Lawrence), the 20S Proteasome (with Drs. Said Sebti and Mark McLaughlin), MDM2 p53 and MDMX-P53 (with Drs. Jiandong Chen and Mark McLaughlin) and Shp2 (with Drs. Jerry Wu and Nick Lawrence).
We are also interested in developing enhanced methods for the docking of inhibitors into protein binding sites and in applying computational techniques to the problem of elucidating the mechanistic details of enzyme catalysis and in the design, synthesis, and study of model complexes that mimic zinc metallproteases.