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http://dx.doi.org/10.5483/BMBRep.2012.45.5.275

Molecular docking study on the α3β2 neuronal nicotinic acetylcholine receptor complexed with α-Conotoxin GIC  

Lee, Che-Wook (Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Lee, Si-Hyung (Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Kim, Do-Hyoung (Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Han, Kyou-Hoon (Biomedical Translational Research Center, Korea Research Institute of Bioscience and Biotechnology)
Publication Information
BMB Reports / v.45, no.5, 2012 , pp. 275-280 More about this Journal
Abstract
Nicotinic acetylcholine receptors (nAChRs) are a diverse family of homo- or heteropentameric ligand-gated ion channels. Understanding the physiological role of each nAChR subtype and the key residues responsible for normal and pathological states is important. ${\alpha}$-Conotoxin neuropeptides are highly selective probes capable of discriminating different subtypes of nAChRs. In this study, we performed homology modeling to generate the neuronal ${\alpha}3$, ${\beta}2$ and ${\beta}4$ subunits using the x-ray structure of the ${\alpha}1$ subunit as a template. The structures of the extracellular domains containing ligand binding sites in the ${\alpha}3{\beta}2$ and ${\alpha}3{\beta}4$ nAChR subtypes were constructed using MD simulations and ligand docking processes in their free and ligand-bound states using ${\alpha}$-conotoxin GIC, which exhibited the highest ${\alpha}3{\beta}2$ vs. ${\alpha}3{\beta}4$ discrimination ratio. The results provide a reasonable structural basis for such a discriminatory ability, supporting the idea that the present strategy can be used for future investigations on nAChR-ligand complexes.
Keywords
${\alpha}$-Conotoxin GIC; Homology modeling; Ligand-docking; Molecular dynamics (MD) simulations; Nicotinic acetylcholine receptors (AChRs);
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