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Title

In silico modeling of ligand molecule for non structural 3 (NS3) protein target of flaviviruses

 

Authors

Shefali Agnihotri*, Ranjana Narula, Kaishiv Joshi, Sandeep Rana & Maneet Singh

 

Affiliation

Department of Bioinformatics, ADI Biosolution, Mohali, India 160059.

 

Email

agnihotri.shefali02@gmail.com ; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received December 30, 2011; Accepted January 07, 2012; Published February 03, 2012

 

Abstract

Flaviviruses are small, enveloped RNA viruses which cause a variety of diseases into animals and man. Despite the existence of licensed vaccines, yellow fever, Japanese encephalitis and tick-borne encephalitis also claim many thousands of victims each year across their vast endemic areas. A number of studies have already revealed that the non-structural NS3 serine protease is required for the maturation of the viral polyprotein and thus is a promising target for the development of antiviral inhibitors. Hence, the 3D structure of NS3 protein was modeled using homology modeling by MODELLER 9v7. Validation of the constructed NS3 protein models were done by PROCHECK, VERYFY3D and through ProSA calculations. Ligands for the catalytic triad (H51, D75, and S135) were designed using LIGBUILDER. The NS3 proteinís catalytic triad was explored to find out the interactions pattern for inhibitor binding using molecular docking methodology using AUTODOCK Vina. The interactions of complex NS3protein-ligand conformations, including hydrogen bonds and the bond lengths were analyzed using Accelrys DS Visualizer software. Hence, from this observation, the novel molecule designed was observed to be the best ligand against the NS3 protein of flavivirus. This molecule may prove to be a potential identity in modulating disease manifestation for all the selected flavivirus members.

 

Keywords

NS3 protein, homology modeling, virtual screening, docking, ligand

 

Abbreviations

NCBI; National Centre for Biotechnological Information, BLAST; Basic Local Alignment Search Tool, DOPE, Discrete optimized protein energy; GROMOS96, GROningen MOlecular Simulation package, SAVS; Structure Analysis and Validation Server.

 

Citation

Agnihotri et al. Bioinformation 8(3): 123-127(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.