Research in the Tonge Group is focused on understanding how proteins control and modulate the properties of small molecule ligands. We are interested in understanding the fundamental aspects of enzyme catalysis and in determining how enzymes cause and stabilize charge rearrangement. Some of the enzymes we study are known or putative drug targets in pathogens such as Mycobacterium tuberculosis, Francisella tularensis , and methicillin-resistant Staphylococcus aureus (MRSA), and for these systems we use mechanistic information to design and synthesize high affinity enzyme inhibitors. In addition to enzymes, we are also interested in understanding how fluorescent proteins, such as green fluorescent protein (GFP), control the formation and fluorescence of the embedded chromophore. Studies on GFP are now being extended to other light activated proteins such as AppA, a BLUF domain antirepressor from the photosynthetic bacterium Rhodobacter sphaeroides.