Faculty Sponsor: Erika Taylor
Live Poster Session: Zoom Link
Gram-negative bacteria are a unique group of bacteria that pose a special health risk due to their double layer membrane. Some examples include E.coli, K. pneumoniae, and H.pylori. The outer layer of Gram-negative bacteria is covered in lipopolysaccharides (LPS) that protect the bacteria from many common antibiotics, making them harder to treat. This increased resistance, however, can be bypassed via inhibition of the protein Heptosyltransferase I (HepI). HepI is responsible for catalyzing the addition of the first heptose moiety to the inner core of LPS and serves as a promising drug target—HepI knockouts show increased antibiotic vulnerability due to their truncated LPS. Previous Taylor Lab studies used AutoDock Vina to filter the National Cancer Institute’s Natural Products Set IV to identify potential inhibitors through molecular docking. The previous study identified 19 ligands that show a particularly strong binding affinity to HepI to test as potential inhibitors and 10 with especially low binding affinities serving as controls. The ligands were evaluated using coupled assays to calculate the dissociation constant (Ki) between HepI and each ligand. The experimental results, however, did not match the computed predictions, with there being little correlation between the two. In order to identify better inhibitors, all of the docking simulations have been rerun in Schrodinger Glide and Prime to confirm whether the error was in AutoDock Vina or the experimental procedure, as well as further narrow down the search for HepI inhibitors. The coupled assays are being rerun with the newly identified ligands to rule out experimental error. Additionally, the compounds have been analyzed for their drug like properties, including quantitative drug likeness (QED), synthetic accessibility score (SAS), and log p, to determine their feasibility as real-world drugs.
poster_gorman_3