AMP-Kinase (AMPK) is the master sensor for the organism’s metabolism and energy, and has many diseases linked to both its activation and inhibition, including cancer, gastrointestinal, heart, and even neurodegenerative diseases. My main research project involves designing and synthesizing potent activators selective for α1β1γ1 and α2β1γ1 isoforms. The gene encoding the β1 subunit of AMPK, PRKAB1, was first discovered as a viable drug target for inflammatory bowel disease (IBD) by our collaborators, the Ghosh lab (UCSD School of Medicine). Using Boolean implication networks to analyze gene clusters, the continuum states of IBD-related diseases were more easily differentiated between disease and health states of patients. Recent efforts in medicinal chemistry in collaboration with the Ghosh lab has opened up some exciting new opportunities in drug design to target proteins such as APMK. Using in silico docking experiments, along with previously published ligand-protein pair co-crystal structures as references, we were able to create a robust model for predicting the binding affinity and selectivity for novel β1 selective agonists. I have established the chemistry and methodology for synthesizing these agonists, and intend to both synthesize and test (in vitro) these novel β1 selective agonists designed in silico.

The video of this presentation is available here.