Bio Chem Press  Internet Electronic Journal of Molecular Design is a refereed journal for scientific papers regarding all applications of molecular design
Home | News | Current Issue | Journal Index | IECMD 2004 | Preprint Index | Instructions for Authors | Send the Manuscript | Special Issue
 BioChemPress.com  To bookmark this site press Ctrl D
 
   Home
   News & Announcements
  Journal Info
   Current Issue
   Journal Index
   Preprint Index
   Editor
   Advisory Board
  Conference Info
   IECMD 2004
   Day 1
   Day 2
   Day 3
   Day 4
   Day 5
   Day 6
   Day 7
   Day 8
   Day 9
   Day 10
   IECMD 2003
  BioChem Links
   CoEPrA
   Support Vector Machines
  Author Info
   Instructions for Authors
   Send the Manuscript
   Special Issue
  Contact
   Editorial Office
   Subscription
   Advertising
   Copyright
  User Info
   Terms of Use
   License

Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
ABSTRACT - Internet Electron. J. Mol. Des. January 2008, Volume 7, Number 1, 12-29

Comparative Modeling and Docking Studies of Mycobacterium tuberculosis H37RV rpoB Protein
P. Nataraj Sekhar, P. B. Kavi Kishor, V. C. K. Reddy, E. Prem Kumar, A. Anitha, Ranjith Kumar M., and L. Ananda Reddy
Internet Electron. J. Mol. Des. 2008, 7, 12-29

Free: Download the paper in PDF format Return to Table of Contents Get Acrobat Reader to view and print the paper

Abstract:
Recently the entire rpoB genes of Mycobacterium leprae and M. tuberculosis have been sequenced and several mutations associated with rifampin resistance have been identified in both species. Since no crystal structure was available for the rpoB protein, a three-dimensional (3D) structure of rpoB protein (a protein complex involved in the polymerization of ribonucleotides) was generated computationally in order to understand the mechanisms of ligand binding and the interactions between the ligand and the protein. Docking experiments for rpoB were performed with its inhibitors to better understand the drug interactions and rifampin resistance, thus allowing us to predict the mutations with respect to the active site of the enzyme and its inhibitor and binding domain. This study may thus help in the development of rapid diagnostic tests for tuberculosis. A three-dimensional model of the rpoB protein (NP_215181) is generated based on the crystal structure of the Thermus thermophilus (PDB: 2CW0) by using the software MODELLER6v2. The structure having the lowest score was used as starting point for further minimization computations. The structure having the lowest energy generated by the conjugate gradient energy minimization, with less than 0.05 kcal/mol energy gradient, was further assessed by PROCHECK, which showed that the refined model is reliable. In order to understand the mechanisms of ligand binding and the interaction between the ligand and the rpoB protein complex, a flexible docking study was performed using GOLD software. Docking results indicated that the fourth binding pocket falls in the active site of the protein. They also indicated that ciprofloxacin is the more preferred inhibitor and that the residues Gln429, Arg448, Ser450 are determinant residues in binding as they have strong hydrogen bonding contacts with the ligand. Thus, this study is useful for the synthesis of novel rpoB inhibitors. Based on docking studies, the bioactive conformations of the ligands obtained will be useful in building structure-based 3-D QSAR models. Our results indicate that ciproflaxin is the best inhibitor against rifampicin resistant rpoB protein.

Free: Download the paper in PDF format Return to Table of Contents Get Acrobat Reader to view and print the paper

Home | News | Current Issue | Journal Index | IECMD 2004 | Preprint Index | Instructions for Authors | Send the Manuscript | Special Issue
Last changes: January 5, 2006 Webmaster
http://www.biochempress.com/
Copyright © 2001-2006 Ovidiu Ivanciuc