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Title

High Throughput Virtual Screening to Identify Novel natural product Inhibitors for MethionyltRNA-Synthetase of Brucella melitensis

 

Authors

Madhulata Kumari1,4 Subhash chandra2 Neeraj Tiwari3 & Naidu Subbarao4*

 

Affiliation

1Department of Information Technology, Kumaun University, SSJ Campus, Almora, Uttarakhand 263601, India

2Department of Botany, Kumaun University, SSJ Campus, Almora, Uttarakhand 263601, India -3Department of Statistics, Kumaun University, SSJ Campus Almora, Uttarakhand, 263601, India. 4School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
 

Email

Email Id: mchandra724@gmail.com;  Email Id: scjnu@yahoo.co.in; Email Id:
kumarn_amo@yahoo.com; Email Id: nsrao@mail.jnu.ac.in; *Corresponding Author

 

Article Type

Hypothesis

 

Date

Received September 9, 2016; Accepted November 5, 2016; Published January 20, 2017

 

Abstract

The Brucella melitensis methionyl-tRNA-synthetase (MetRSBm) is a promising target for brucellosis drug development. The virtual screening of large libraries of a drug like molecules against a protein target is a common strategy used to identify novel inhibitors. A High throughput virtual screening was performed to identify hits to the potential antibrucellosis drug target, MetRSBm. The best inhibitor identified from the literature survey was 1312, 1415, and 1430. In the virtual screening 56,400 compounds of ChEMBL antimycobacterial library, 1596 approved drugs, 419 Natural product IV library, and 2396 methionine analogous were docked and rescoring, identified top 10 ranked compounds as anti-mycobacterial leads showing G-scores -10.27 to -8.42 (in kcal/mol), approved drugs G-scores -9.08 to -6.60 (in kcal/mol), Natural product IV library G-scores -10.55 to -6.02 (in kcal/mol), methionine analogous Gscores -11.20 to -8.51 (in kcal/mol), and compared with all three known inhibitors (as control) G-scores -3.88 to -3.17 (in kcal/mol). This result indicates these novel compounds have the best binding affinity for MetRSBm. In this study, we extrapolate that the analogous of methionine for find novel drug likeness has been identified [4-(L-histidyl)-2-phenylbenzoyl] methionine hydrochloride, might show the inhibitor of Brucella melitensis effect by interacting with MetRS enzyme. We suggests that Prumycin as a natural product is the novel drugs for brucellosis.

 

Keywords

Brucella melitensis, Methionyl-tRNA-Synthetase, Molecular docking, HTVS

 

Citation

Kumari et al. Bioinformation 13(1): 8-16 (2017)

 

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.