Publication Type:

Journal Article


Interdisciplinary Sciences: Computational Life Sciences, Volume 4, Number 3, p.223-238 (2012)



Amino Acid, amino acid sequence, article, chemistry, drug antagonism, enzymology, glutamic acid, metabolism, molecular dynamics, Molecular Dynamics Simulation, molecular genetics, Molecular Sequence Data, Mycobacterium tuberculosis, peptide synthase, Peptide Synthases, sequence homology, UDP N acetylmuramoylalanine D glutamate ligase, UDP-N-acetylmuramoylalanine-D-glutamate ligase


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


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Cite this Research Publication

Aad Arvind, Kumar, Va, Saravanan, Pb, and Dr. Gopi Mohan C., “Homology modeling, molecular dynamics and inhibitor binding study on MurD ligase of Mycobacterium tuberculosis”, Interdisciplinary Sciences: Computational Life Sciences, vol. 4, pp. 223-238, 2012.