The primary emphasis of our research focuses on developing an understanding of enzymatic reactions and receptor-ligand interactions at a molecular level. The approach is to use a combination of kinetic and structural techniques including rapid transient kinetics, NMR, mass spectrometry and X-Ray crystallography. This allows a quantitative and structural basis for understanding how proteins work at a molecular level. The structure-based drug design in conjunction with combinatorial library screening methods provide a powerful advance in identifying lead compounds. Our ultimate goal in this research is to develop an in-depth mechanistic understanding of how enzymes function and thereby provide a more effective means of modulating their function.
We are using this approach to examine the mechanisms of several enzymes which are important targets for the development of therapeutics. These enzymes include tryptophan synthase and KDO8P synthase which may be important targets for new antibacterials. In addition, a bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) enzyme from parasites also may be a target for new antiparasitic drugs. Also ongoing are mechanistic studies on HER-2 tyrosine kinase, a potential target for drugs to treat breast cancer. Finally, we are also studying the mechanisms of HIV reverse transcriptase as well as drug resistance which may ultimately aid in the design of better therapeutic agents for the treatment of AIDS.