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Title

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

 

Authors

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

 

Affiliation

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

s.jayachandran@bdu.ac.in; *Corresponding author

 

Article Type

Hypothesis

 

Date

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

 

Abstract

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.

 

Keywords

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

 

Citation

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

Edited by

P Kangueane

 

ISSN

0973-2063

 

Publisher

Biomedical Informatics

 

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.