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 13 (1):59-79, 2012.

Molecular modelling and docking of Brugia malayi glutathione reductase


Sudhanshu Shekhar Yadav1*, Vinay Kumar Singh2, Eva Liebau3, Sushma Rathaur1


1Department of Biochemistry, 2Centre for Bioinformatics, Faculty of Science, Banaras Hindu University, Varanasi 221005, U.P., India 3Westfalische Wilhelms-Uinversitat, Institute of Animal Physiology, Department of Molecular Physiology, Hindenburgplatz-55, Muenster, Germany




Yadav SS, Singh VK, Liebau E, Rathaur S., Molecular modelling and docking of Brugia malayi glutathione reductase, Online J Bioinform, 13 (1):59-79, 2012. Brugia malayi Glutathione Reductase (BmGR), a redox enzyme that reduces glutathione disulfide (GSSG) to the sulfhydryl form GSH plays an important role in filariasis and other diseases. BmGR was modeled using a 3DK9 template with 324 hydrogen Bonds, 18 helices, 32 strands and 47 turns and accepted at PMDB database (PM0077742). The model was used to dock and simulate the antifilarial drugs diethylcarbamazine citrate and albendazole, specific inhibitors of GR; 3,4 Dihydroxybenzyleamine and 1,3-bis(2-chloroethyl)-1-nitrosourea and substituted chalcones (SK series compounds). The active site analysis alignment of HsGR revealed ten stretches as active binding sites in BmGR. The amino acid residues SER19, GLU39, GLU40, THR41, THR46, TYR146, ASP162, ARG267, ARG272, ASP307 and THR315 were involved in hydrogen bonding, hydrophobic, polar, cation-pi and other interactions with NADPH. The binding of GSSG with protein especially with amino acids ALA142 and VAL143 and overlapped with NADPH binding site except SER19, ARG267, ARG272, ASP307 and THR315. In-silico investigation revealed that interaction of DEC with amino acids TYR181, ILE182 & ASP307 and SER19, THR46, ALA142, VAL143 & ALA318 interacting with ALB and specific inhibitors; DHBA showing interaction with amino acids GLU39, GLU40, THR41, THR46 & THR146 and SER19, GLY20 & THR46 with BCNU are involved in hydrogen, hydrophobic and polar level interactions. However, the interaction sites of antifilarials are similar to the binding sites of GSSG but positions are different and the binding sites of specific inhibitors are similar to the substrate i.e. active site domain II of BmGR protein. While SK series compounds are interact with highest coordination of the major portion of the active binding site as well as NADPH binding site of the protein. Based on estimated free energy of binding, lowest inhibition constant (Ki) and lower frequency percentage ALB, BCNU and substituted chalcones were showing better interactions. Specific inhibitors are showing competitive type binding (stretch 1 & 2) with substrate while substituted chalcones non-competitive (stretch 1, 2, 3 & 6). However, Stretch 5 and 7 may be the activator sites of the protein, which are the binding sites of antifilarials. Amino acids SER19, CYS47, CYS52 and PHE165 may be better inhibitory sites for drug designing using BmGR as template. Among substituted chalcone SK-3 and SK-5 are showing lower estimated free energy of binding, lowest inhibition constant (Ki) and lower frequency percentage. These substituted chalcones may be good inhibitors of glutathione metabolism and have better antifilarial activity. The BmGR structural information and docking studies could aid in screening new antifilarials or selective inhibitors for chemotherapy against filariasis.


Key Words: DEC; Diethylcarbamazine citrate, ALB; Albendazole, DHBA; 3,4 Dihydroxybenzyleamine, BCNU; 1,3-bis(2-chloroethyl)-1-nitrosourea, Substituted chalcones, filariasis.