Achievement

David Rooklin, in collaboration with his advisor Yingkai Zhang (Chemistry), is interested in understanding the mechanism, specificity, and catalytic power behind enzymatic phosphoryl transfer in various medically relevant biochemical systems. The two systems under study are protein tyrosine phosphatase 1B (PTP1B), important for its role in squelching insulin signaling, and soluble calcium-activated nucleotidase 1 (SCAN-1), attractive as a potential antithrombotic agent. He has employed ab initio QM/MM molecular dynamics to simulate protein/substrate complexes of these enzymes. Regarding PTP1B, he has used free energy calculations to study the details of its reactant state and catalytic mechanism, resolving some existing debate within the literature. Regarding SCAN-1, he has begun to investigate its experimentally observed substrate specificity for GDP.