Homology modeling, molecular dynamics and inhibitor binding study on MurD ligase of Mycobacterium tuberculosis

  • Akanksha Arvind
  • Vivek Kumar
  • Parameswaran Saravanan
  • C. Gopi Mohan


The cell wall of mycobacterium offers well validated targets which can be exploited for discovery of new lead compounds. MurC-MurF ligases catalyze a series of irreversible steps in the biosynthesis of peptidoglycan precursor, i.e. MurD catalyzes the ligation of D-glutamate to the nucleotide precursor UMA. The three dimensional structure of Mtb-MurD is not known and was predicted by us for the first time using comparative homology modeling technique. The accuracy and stability of the predicted Mtb-MurD structure was validated using Procheck and molecular dynamics simulation. Key interactions in Mtb-MurD were studied using docking analysis of available transition state inhibitors of E.coli-MurD. The docking analysis revealed that analogues of both L and D forms of glutamic acid have similar interaction profiles with Mtb-MurD. Further, residues His192, Arg382, Ser463, and Tyr470 are proposed to be important for inhibitor-(Mtb-MurD) interactions. We also identified few pharmacophoric features essential for Mtb-MurD ligase inhibitory activity and which can further been utilized for the discovery of putative antitubercular chemotherapy.

Key words

Mtb-MurD homology modeling molecular dynamics molecular docking chemotherapy peptidoglycan resistance protein structure 





Mycobacterium tuberculosis


UDP-N-acetylmuramoyl-L-alanine-D-glutamate ligase




directly observed treatment short course


World Health Organization






molecular dynamics


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Supplementary material

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Copyright information

© International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Akanksha Arvind
    • 1
  • Vivek Kumar
    • 1
  • Parameswaran Saravanan
    • 2
  • C. Gopi Mohan
    • 3
  1. 1.Department of PharmacoinformaticsNational Institute of Pharmaceutical Education and Research (NIPER)S.A.S. NagarIndia
  2. 2.Department of BiochemistryIndian Institute of TechnologyGuwahatiIndia
  3. 3.Amrita Centre for Nanosciences and Molecular Medicine (ACNSMM), Amrita Institute of Medical Sciences & Research CentreAmrita Vishwa Vidyapeetham UniversityPonekkara, KochiIndia
  4. 4.Department of Medicinal ChemistryUniversity of Illinois at ChicagoChicagoUSA

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