1996-2019. All Rights Reserved. Online Journal of Bioinformatics . You may not store these pages in any form except for your own personal use. All other usage or distribution is illegal under international copyright treaties. Permission to use any of these pages in any other way besides the  before mentioned must be gained in writing from the publisher. This article is exclusively copyrighted in its entirety to OJB publications. This article may be copied once but may not be, reproduced or  re-transmitted without the express permission of the editors. This journal satisfies the refereeing requirements (DEST) for the Higher Education Research Data Collection (Australia). Linking: To link to this page or any pages linking to this page you must link directly to this page only here rather than put up your own page.


 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




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