STRUCTURE BASED DISCOVERY OF INHIBITORS FOR MULTIDRUG EFFLUX PUMP- ACRB

In Escherischia coli, AcrB is an inner membrane transporter that cooperates with a membrane fusionprotein, AcrA and an outer membrane channel TolC, to export a wide variety of drugs directly out of the cell, bypassing the periplasm. By overproducing such membrane transport proteins, E. coli and other human pathogenic bacteria are able to achieve multidrug resistance. In this paper, we have reported the virtual screening of five in silico small molecule libraries against the substrate recognition site situated in the porter domain of binding protomer of AcrB using tools of Schrödinger suite, which resulted in six potential hits. All these compounds favored hydrogen bonding interactions with mainly polar and aromatic residues such as Ser134, Phe178 and Ile671. From the observed results these ligands are suggested to be potent candidates for inhibiting AcrB. Docking simulations were also carried out with several known substrates and inhibitors in order to study their interactions with the binding site.