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J Mol Graph Model. 2010 Jan;28(5):435-45. doi: 10.1016/j.jmgm.2009.10.003. Epub 2009 Oct 31.

Structural modeling and simulation studies of Brugia malayi glutathione-S-transferase with compounds exhibiting antifilarial activity: implications in drug targeting and designing.

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1
Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, U.P., India.

Abstract

Since glutathione-S-transferase (GST) mediated xenobiotic detoxification is a crucial mechanism in nematodes survival, we aimed to conduct an in silico analysis of filarial GST in order to predict the possible interactions for antifilarials. Present report depicts the homology modeling approach applied in the construction of molecular structure of Brugia malayi GST (BmGST) followed by its docking simulation with available antifilarials such as diethylcarbamazine, albendazole, Butylated Hydroxyanisole (BHA) and substituted chalcones. A very low root mean square deviation (0.82A) from template structure and stereochemical quality of constructed BmGST model proposed it as a significant framework for further analysis. In docking studies antifilarials and chalcones exhibited demarcation in their binding affinity and modes. Amongst all the compounds studied, albendazole and methyl-substituted chalcone showed the lowest binding energy and occupied binding pocket near to substrate binding site of GST. The side chain of these compounds interplayed as a potential interaction site which targeted mainly hydrophilic residues of the BmGST. The structural information and binding site mapping of BmGST for different antifilarials obtained from this study could aid in screening and designing new antifilarials or selective inhibitors for chemotherapy against filariasis.

PMID:
19963420
DOI:
10.1016/j.jmgm.2009.10.003
[Indexed for MEDLINE]

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