KMID : 0624620120450050275
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BMB Reports 2012 Volume.45 No. 5 p.275 ~ p.280
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Molecular docking study on the ¥á3¥â2 neuronal nicotinic acetylcholine receptor complexed with ¥á-Conotoxin GIC
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Lee Che-Wook
Lee Si-Hyung Kim Do-Hyoung Han Kyou-Hoon
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Abstract
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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. ¥á-Conotoxin neuropeptides are highly selective probes capable of discriminating different subtypes of nAChRs. In this study, we performed homology modeling to generate the neuronal ¥á3, ¥â2 and ¥â4 subunits using the x-ray structure of the ¥á1 subunit as a template. The structures of the extracellular domains containing ligand binding sites in the ¥á3¥â2 and ¥á3¥â4 nAChR subtypes were constructed using MD simulations and ligand docking processes in their free and ligand-bound states using ¥á-conotoxin GIC, which exhibited the highest ¥á3¥â2 vs. ¥á3¥â4 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.
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KEYWORD
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¥á-Conotoxin GIC, Homology modeling, Ligand-docking, Molecular dynamics (MD) simulations, Nicotinic acetylcholine receptors (nAChRs)
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