Title

Authors

Affiliation

¹Madhav Institute of Technology Science, Gwalior, Madhya Pradesh-474005; ²Acharya Narendra Dev College, University of Delhi; 3Jawaharlal Nehru University, New Delhi -110067

Email

andrew@jnu.ac.in; *Corresponding author

Article Type

Hypothesis

Date

Received November 15, 2014; Accepted November 17, 2014; Published November 27, 2014

The Mur E enzyme of Mur pathway of Mycobacterium tuberculosis is an attractive drug target as it is unique to bacteria and is absent in mammalian cells. The virtual screening of large libraries of drug like molecules against a protein target is a common strategy used to identify novel inhibitors. However, the method has a large number of pitfalls, with large variations in accuracy caused in part by inaccurate protocols, use of improper standards and libraries, and system dependencies such as the potential for non-specific docking from large active-site cavities. The screening of drug-like small molecules from diversity sets can, however, be used to short-list potential fragments as building blocks to generate leads with improved specificity. We describe a protocol to implement this strategy, which involves an analysis of the active site and known inhibitors to identify orthospecific determinants, virtual screening of a drug-like diversity library to identify potential drug primitives, and inspection of the potential docked fragments for both binding potential and toxicity. The protocol is implemented on the M.tb Mur E protein which has a large active site with poor enrichment of known positives and a set of drug-like molecules that meets this criteria is presented for further analysis.

Keywords

PDB ID: 2XJA; Mycobacterium tuberculosis; Virtual Screening; Molecular Docking; Mur E inhibitors.

Abbreviations

MTB-Mycobacterium tuberculosis; NCI- National Cancer Institute; PDB- Protein Databank.

Citation

Singh et al. Bioinformation 10(11): 697-702 (2014)
 

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.