title: Virtual screening of specific chemical compounds by exploring E.coli NAD+-dependent DNA ligase as a target for antibacterial drug discovery.
abstract: Unique substrate specificity compared with ATP-dependent human DNA ligases recommends E.coli NAD(+)-ligases as potential targets. A plausible strategy is to identify the structural components of bacterial DNA ligase that interact with NAD(+) and then to isolate small molecules that recognize these components and thereby block the binding of NAD(+) to the ligase. This work describes a molecular modeling approach to detect the 3D structure of NAD(+)-dependent DNA ligase in E. coli whose partial structure was determined by wet lab experiments and rest structure was left as such on the road for repairment. We applied protein-drug docking approach to detect the binding affinity of this enzyme with Quinacrine and some of its virtual derivatives. In silico docking results predict that the virtual derivative of Quinacrine (C21H26ClN3O2) has greater binding affinity than Quinacrine. Drug likeness value of 0.833 was observed for this derivative without showing any toxicity risk.
authors.affiliation: Department of Bioinformatics, Dolphin Post Graduate College of Life Sciences, Punjabi University, Patiala, Punjab, India. bashirakhlaq@gmail.com
authors.forename: Bashir Akhlaq
authors.initials: BA
authors.lastname: Akhoon
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Gagan
authors.initials: G
authors.lastname: Dhaliwal
authors.forename: Mugdha
authors.initials: M
authors.lastname: Srivastava
authors.forename: Shailendra K
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D011088:DNA Ligases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D055808:Drug Discovery; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D008958:Models, Molecular; D009243:NAD / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011796:Quinacrine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology; D017421:Sequence Analysis
chemical_list: D000900:Anti-Bacterial Agents; D011804:Quinolines; D009243:NAD; D011088:DNA Ligases; C120640:DNA ligase (NAD); D011796:Quinacrine