College of Pharmacy
This laboratory combines bench work, bioinformatics, and molecular modeling to understand protein structure, protein-protein interaction, and protein-ligand interaction thermodynamics. They are currently working primarily on projects including modeling and redesign of anti-cancer agents targeted toward the MCT 1 and 4 transporters at the cell surface and the mitochondrial pyruvate carrier (MPC) within the mitochondrial membrane. This includes building models of the transporters themselves and computationally docking novel anti-cancer agents onto them. Results can then be used to iteratively improve drug characteristics and binding affinity. Refinement of these steps also includes short run molecular dynamics simulations and collective structure activity relationship analysis and pharmacophore generation of promising drug candidates.
The lab has recently begun a collaborative project modeling the respiratory and glycolytic proteins of Trypanosoma brucei and Trypanosoma cruzi to understand their regulation and unique structure-function characteristics. The phylogenetic uniqueness of these respiratory and glycolytic proteins may offer a novel drug targeting opportunity against these disease causing parasites. Again, these projects are informed by bioinformatic and phylogenetic analysis as well as protein molecular dynamics and computational ligand/drug docking. The researchers have begun to collect preliminary kinetic data on the phosphofructokinase enzyme from these organisms using a heterologous gene expression system. The laboratory results will be interpreted and combined with computational analysis to characterize the novel properties of the PFK enzymes with respect to other eukaryotic and prokaryotic orthologs.