AI-Enabled Design of Peptidomimetics and Small Molecules Targeting Klebsiella pneumoniae

Gaurav Bhardwaj along with collaborators Joshua Woodward and Frank DiMaio all of the University of Washington in the U.S. will leverage recent advances in deep learning methods to build an AI-enabled platform for designing peptidomimetics and small-molecule inhibitors of essential bacterial proteins. The team will pursue three complementary strategies in parallel to design new antibiotic candidates against Klebsiella pneumoniae. First, they will redesign natural products into more stable, synthetically-accessible peptidomimetics. In parallel, they will use AI-enabled methods to de novo design new direct-acting inhibitors of critical bacterial proteins. Finally, the team will use bioactive macrocyclic peptides to identify potent small molecule inhibitors of bacterial proteins critical for growth and survival. Together, these approaches will establish a broadly applicable platform for the rapidly generating customized antibiotic candidates against a range of targets and bacterial pathogens.

This grant is funded by The Novo Nordisk Foundation.