in Silico analysis of Escherichia coli polyphosphate kinase (PPK) as a novel antimicrobial drug target and its high throughput virtual screening against PubChem library

摘要

Multiple drug resistance (MDR) in bacteria is a global health challenge that needs urgent attention. The 2011 outbreak caused by Escherichia coli O104:H4 in Europe has exposed the inability of present antibiotic arsenal to tackle the problem of antimicrobial infections. It has further posed a tremendous burden on entire pharmaceutical industry to find novel drugs and/or drug targets. Polyphosphate kinase (PPK) in bacteria plays a crucial role in helping latter to adapt to stringent conditions of low nutritional availability thus making it a good target for antibacterials. In spite of this critical role, to best of our knowledge no in-silico work has been carried out to develop PPK as an antibiotic target. In the present study, virtual screening of PPK was carried out against all the 3D compounds with pharmacological action present in PubChem database. Our screening results were further refined by interaction maps to eliminate the false positive data respectively. From our results, compound number 5281927 (PubChem ID) has been found to have significant affinity towards affinity towards PPK active ATP-binding site indicating its therapeutic relevance.