Sako Mirzaie
Islamic Azad University, Iran
Title: Structure-based virtual screening to identify the ï¢-lactamase CTX-M-9 inhibitors: An in silico effort to overcome antibiotic resistance in E. coli
Biography
Biography: Sako Mirzaie
Abstract
Recently, the quick spreads of broad-spectrum b-lactams antibiotic resistance in pathogenic strains of bacteria has become a major global health problem. These new emerging resistances cause ineffectiveness of antibiotics and increasing the severity of diseases and treatment costs. Among different and diverse resistance targets, we chose a class-A b-lactamase, CTX-M-9, with the aim of identifying new chemical entities to be used for further rational drug design. Based on this purpose, a set of 5000 molecules from the Zinc database have been screened by docking experiments using AutoDock Vina software. The best ranked compound with respect of the previously proved inhibitor compound 19 was further tested by molecular dynamics (MD) simulation. Our molecular modeling analysis demonstrates that ZINC33264777 has ideal characteristics a potent b-lactamase CTX-M-9 inhibitor. In the free form of b-lactamase, NMR relaxation studies showed the extensive motions near the active site and in the Ω-loop. However, our molecular dynamics studies revealed that in the compound 1: b-lactamase complex, the flexibility of Ω-loop was restricted.