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

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. [BMB Reports 2012; 45(5): 275-280]