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OJBTM

 Online Journal of Bioinformatics © 

  Volume 14 (3): 282-292, 2013

Virtual dihydroxy acid dehydratase inhibitors for tuberculosis

 

Jena L1,2, Kumar S1*

 

1Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences,  Sevagram, Maharashtra and 2Department of Bioinformatics, Shri JJT University, Jhunjhunu, Rajasthan, India

 

ABSTRACT

 

Jena L, Kumar S., Virtual dihydroxy acid dehydratase inhibitors for tuberculosis, Onl J Bioinform., 14 (3): 282-292, 2013. Dihydroxy acid dehydratase (DHAD) encoded by the gene Rv0189c is essential for  biosynthesis of BCAA and pantothenate (coenzyme A) in Mycobacterium tuberculosis (MTB). A 3D model of DHAD was built using Phyre 2 server followed by structural refinement and energy minimization by YASARA Energy Minimization server. The refined model reliability was assessed through Procheck, ProSA and ProQ. A dataset of 135 Drug like compounds were retrieved from ZINC database based on the properties similar to the DHAD natural substrate 2,3-dihydroxy-3-methylbutanoate. Molecular docking program Auto Dock Vina in PyRx 0.8 was applied to identify two drug-like compounds, ZINC40397312 (1-(1H-1,2,3,4-tetrazol-5-yl)cyclobutan-1-amine) and ZINC00330490 (6-hydroxy-2-(methylamino)-3,4-dihydropyrimidin-4-one) as potential inhibitors against DHAD of MTB. The docking result was verified by molecular dynamics simulations. The inhibitors might be useful for design of drugs targeting BCAA biosynthesis.

 

Keywords: BCAA Biosynthesis, DHAD, tuberculosis, virtual screening, inhibitors

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