Binding mode prediction of biologically active compounds from plant <i>Salvia Miltiorrhiza</i> as integrase inhibitor

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Title	*Binding mode prediction of biologically active compounds from plant Salvia Miltiorrhiza* as integrase inhibitor**
Authors	Nadtanet Nunthaboot¹*, Kiattisak Lugsanangarm², Sirirat Kokpol² & Ibrahim S Abd-Elazem³
Affiliation	¹Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Mahasarakham University, Mahasarakham,44150, Thailand; ²Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand; ³Department of Biology, The Johns Hopkins University, Baltimore, Maryland, 21218, USA
Email	nadtanet@gmail.com; *Corresponding author
Article Type	Hypothesis
Date	Received March 30, 2013; Accepted 01, 2013; Published April 30, 2013
Abstract	Integrase (IN), an essential enzyme for HIV-1 replication, has been targeted in antiretroviral drug therapy. The emergence of HIV-1 variants clinically resistant to antiretroviral agents has lead to the development of alternative IN inhibitors. In the present work, binding modes of a high potent IN inhibitor, M₅22 and M₅32, within the catalytic binding site of wild type (WT) IN were determined using molecular docking calculation. Both M₅22 and M₅32 displayed similar modes of binding within the IN putative binding pocket and exhibited favorable interactions with the catalytic Mg²⁺ ions, the nearby amino acids and viral DNA through metal-ligand chelation, hydrogen bonding and p-p stacking interactions. Furthermore, the modes of action of these two compounds against the mutated Y212R, N224H and S217H PFV IN were also predicted. Although the replacement of amino acid could somehow disturb inhibitor binding mode, almost key interactions which detected in the WT complexes were fairly conserved. Detailed information could highlight the application of M₅22 and M₅32 as candidate IN inhibitors for drug development against drug resistant strains.
Keywords	Diabetes, Phytochemicals, Insulin signaling pathway, Phyto Diab Care.
Citation	*Nunthaboot et al.* Bioinformation 9(8): 426-431 (2013)
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.