Investigation of Small Molecules as Periplasmic Chaperone Inhibitors Using In Silico and In VivoMethods

Science Center, Bent Corridor

The proper folding of many outer membrane proteins of E. Coli depends on the activity of the periplasmic chaperones SurA, Skp, and DegP. The importance of chaperones in maintaining the periplasmic proteome suggests small molecules that bind to and inhibit the function of these chaperones could results in inhibited bacterial growth. Our goal is to understand the binding mechanism of not only small molecules but also the client proteins with SurA and other periplasmic chaperones through protein-ligand docking. We used these docking predictions to find drug candidates using virtual screening, and we have begun to test these most promising small molecules through assessment of their bacterial lethality in vivo.