Homology modeling, molecular docking and electrostatic potential analysis of MurF ligase from Klebsiella pneumonia



Venkatabalasubramanian Sivaramakrishnan1, Chinnaiyan Thiyagarajan2, Sivakumaran Kalaivanan2, Raj Selvakumar2, Muthuswamy Anusuyadevi3 & Kesavan Swaminathan Jayachandran2*



1Department of Bioinformatics, School of chemistry and biotechnology, SASTRA University, Thirumalaisamudram, Thanjavur-613402, Tamilnadu, India; 2Department of Bioinformatics, Bharathidasan University, Palkalaiperur, Tiruchirapalli-620024, Tamilnadu, India; 3Department of Biochemistry, Bharathidasan University, Palkalaiperur, Tiruchirapalli-620024, Tamilnadu, India


Email; *Corresponding author


Article Type




Received May 13, 2012; Accepted May 24, 2012; Published May 31, 2012



In spite of availability of moderately protective vaccine and antibiotics, new antibacterial agents are urgently needed to decrease the global incidence of Klebsiella pneumonia infections. MurF ligase, a key enzyme, which participates in the bacterial cell wall assembly, is indispensable to existence of K. pneumonia. MurF ligase lack mammalian vis-ŗ-vis and have high specificity, uniqueness, and occurrence only in eubacteria, epitomizing them as promising therapeutic targets for intervention. In this study, we present a unified approach involving homology modeling and molecular docking studies on MurF ligase enzyme. As part of this study, a homology model of K. pneumonia (MurF ligase) enzyme was predicted for the first time in order to carry out structure-based drug design. The accuracy of the model was further validated using different computational approaches. The comparative molecular docking study on this enzyme was undertaken using different phyto-ligands from Desmodium sp. and a known antibiotic Ciprofloxacin. The docking analysis indicated the importance of hotspots (HIS 281 and ASN 282) within the MurF binding pocket. The Lipinskiís rule of five was analyzed for all ligands considered for this study by calculating the ADME/Tox, drug likeliness using Qikprop simulation. Only ten ligands were found to comply with the Lipinski rule of five. Based on the molecular docking results and Lipinki values 6-Methyltetrapterol A was confirmed as a promising lead compound. The present study should therefore play a guiding role in the experimental design and development of 6-Methyltetrapterol A as a bactericidal agent.



Klebsiella pneumonia, MurF ligase, Homology modeling, Hotspots, 6-Methyltetrapterol A, Electrostatic potenti



Sivaramakrishnan et al. Bioinformation 8(10): 466-473 (2012)

Edited by

P Kangueane






Biomedical Informatics



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