Table of Contents    
ARTICLE
Year : 2011  |  Volume : 2  |  Issue : 3  |  Page : 72-73  

Designing and development of novel antituberculosis drugs by in silico targeting against Decaprenyl-phosphoryl-β-D-ribose oxidase: A structure based drug designing approach


Department of Biochemical Engineering, Banaras Hindu university, UP, India

Date of Web Publication26-May-2012

Correspondence Address:
Richa Anand
Department of Biochemical Engineering, Banaras Hindu university, UP
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


Rights and PermissionsRights and Permissions

How to cite this article:
Anand R. Designing and development of novel antituberculosis drugs by in silico targeting against Decaprenyl-phosphoryl-β-D-ribose oxidase: A structure based drug designing approach. J Nat Sc Biol Med 2011;2, Suppl S1:72-3

How to cite this URL:
Anand R. Designing and development of novel antituberculosis drugs by in silico targeting against Decaprenyl-phosphoryl-β-D-ribose oxidase: A structure based drug designing approach. J Nat Sc Biol Med [serial online] 2011 [cited 2020 Feb 24];2, Suppl S1:72-3. Available from: http://www.jnsbm.org/text.asp?2011/2/3/72/95843

Mycobacterium tuberculosis a causative agent of tuberculosis is gram-positive and slow growing bacterium. Decaprenyl-phosphoryl-β-D-ribose oxidase is an important enzyme involved in the cell wall synthesis of Mycobacterium tuberculosis. It is involved in the epimerization of decaprenyl-phosphoryl-D-ribose into decaprenyl-phosphoryl-D-arabinose, a precursor for arabinan synthesis. Its 3-D structure has not yet been reported either by X-ray crystallography or NMR. Therefore, model of decaprenyl-phosphoryl-β-D-ribose oxidase was determined by homology modeling, using multi-template approach based on crystal structure of 2EXR.pdb and 2Q4W.pdb with score=48.9 bits and identities=42/148 (29%). The computed model was subjected to refinement on the basis of consensus generated from 2D structure. The energy minimization and molecular dynamics simulation was performed by DESMOND using OPLS-AA force field and finally evaluated using SAVES server to obtain reliable structure. The modeled protein was used for structure-based virtual screening against ZINC database through molecular docking using Molegro Virtual Docker (MVD) 4.2.0. Out of 19365 ZINC database molecules, top 10 docked complexes obtained after virtual screening were enumerated and validated based on Molegro Virtual Docker 4.2.0 Scoring function and ADME properties. On the basis of docking energies top 10 ligands were selected for validation using AutoDock/Vina scoring function to compare their results. Thus the complex scoring, docking energies and binding affinities revealed that these ligand molecules could be promising inhibitors for decaprenyl-phosphoryl-beta-D-ribose-2'-oxidase. The docking studies also reveal that Tyr (335), Thr (426) are prominently involved in hydrogen bond interactions with the ligands and thus they are important determinant residues in binding with ligands.




 

Top
  
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article

 Article Access Statistics
    Viewed1034    
    Printed49    
    Emailed0    
    PDF Downloaded208    
    Comments [Add]    

Recommend this journal