A comparative modeling and molecular docking study on Mycobacterium tuberculosis targets involved in peptidoglycan biosynthesis

Zeynab Fakhar, Suhashni Naiker, Claudio N. Alves, Thavendran Govender, Glenn E.M. Maguire, Jeronimo Lameira, Gyanu Lamichhane, Hendrik G. Kruger, Bahareh Honarparvar

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


An alarming rise of multidrug-resistant Mycobacterium tuberculosis strains and the continuous high global morbidity of tuberculosis have reinvigorated the need to identify novel targets to combat the disease. The enzymes that catalyze the biosynthesis of peptidoglycan in M. tuberculosis are essential and noteworthy therapeutic targets. In this study, the biochemical function and homology modeling of MurI, MurG, MraY, DapE, DapA, Alr, and Ddl enzymes of the CDC1551 M. tuberculosis strain involved in the biosynthesis of peptidoglycan cell wall are reported. Generation of the 3D structures was achieved with Modeller 9.13. To assess the structural quality of the obtained homology modeled targets, the models were validated using PROCHECK, PDBsum, QMEAN, and ERRAT scores. Molecular dynamics simulations were performed to calculate root mean square deviation (RMSD) and radius of gyration (Rg) of MurI and MurG target proteins and their corresponding templates. For further model validation, RMSD and Rg for selected targets/templates were investigated to compare the close proximity of their dynamic behavior in terms of protein stability and average distances. To identify the potential binding mode required for molecular docking, binding site information of all modeled targets was obtained using two prediction algorithms. A docking study was performed for MurI to determine the potential mode of interaction between the inhibitor and the active site residues. This study presents the first accounts of the 3D structural information for the selected M. tuberculosis targets involved in peptidoglycan biosynthesis.

Original languageEnglish (US)
Pages (from-to)2399-2417
Number of pages19
JournalJournal of Biomolecular Structure and Dynamics
Issue number11
StatePublished - Nov 1 2016


  • Mycobacterium tuberculosis
  • homology modeling
  • molecular docking
  • molecular dynamics simulation
  • peptidoglycan
  • radius of gyration (Rg)
  • root mean square deviation (RMSD)

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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