Title

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

Authors

Madhulata Kumari^1,4 Subhash chandra² Neeraj Tiwari³ & Naidu Subbarao^4*

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

mchandra724@gmail.com;

scjnu@yahoo.co.in;

kumarn_amo@yahoo.com;

nsrao@mail.jnu.ac.in;

Article Type

Hypothesis

Date

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

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.