Molecular docking study on the alpha3beta2 neuronal nicotinic acetylcholine receptor complexed with alpha-conotoxin GIC.
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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. 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 alpha3, beta2 and beta4 subunits using the x-ray structure of the alpha1 subunit as a template. The structures of the extracellular domains containing ligand binding sites in the alpha3beta2 and alpha3beta4 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 alpha3beta2 vs. alpha3beta4 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. (+info)
Constrained de novo sequencing of conotoxins.
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