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Background: The details of interaction in a complex between potent antagonists such as long chain α-neurotoxins and α-conotoxins with nicotinic acetylcholine receptor (nAChR), and conformational changes induced by these antagonists, are not yet clear. Modeling: In order to uncover some of these critical structural features, we conducted a docking simulation and a molecular dynamics simulation (MD) of a model of the ligand binding domain of nAChR in complex with a long-chain α-neurotoxin and an α-conotoxin. Results: Our docking results confirm the claim that T.nAChR is in the basal or resting state, which favors binding to the alpha-neurotoxins. Moreover, more correct "hits" for the a/γ interface upon docking for conotoxin-nAChR confirm the preference of conotoxin GI for the a/γ interface. More importantly, upon binding of a-neurotoxin, ligand-bonded nAChR is less dynamic in certain domains than the apo form of the conotoxin-AChR complex. Some critical interactions in the binding site such as the salt bridge formed between K145/D200 in the neurotoxin-nAChR complex is further stabilized during the MD simulation, while it is obviously more labile in the apo form. Conclusion: These observations could support the claim that alpha neurotoxins stabilize the nAChR resting state. [ABSTRACT FROM AUTHOR]

An abstract of the article "Binding site locations and interaction of the isolated middle loop of snake neurotoxin I with muscle type nicotinic acetylcholine receptor: molecular dynamics and docking simulation study," by Adak Nasiripourdori, Bijan Ranjbar and Hossein Naderi-Manesh is presented.

Background: The details of interaction in a complex between potent antagonists such as long chain alpha-neurotoxins and alpha-conotoxins with nicotinic acetylcholine receptor (nAChR), and conformational changes induced by these antagonists, are not yet clear. MODELING: In order to uncover some of these critical structural features, we conducted a docking simulation and a molecular dynamics simulation (MD) of a model of the ligand binding domain of nAChR in complex with a long-chain alpha-neurotoxin and an alpha-conotoxin., Results: Our docking results confirm the claim that T.nAChR is in the basal or resting state, which favors binding to the alpha-neurotoxins. Moreover, more correct "hits" for the alpha/gamma interface upon docking for conotoxin-nAChR confirm the preference of conotoxin GI for the alpha/gamma interface. More importantly, upon binding of alpha-neurotoxin, ligand-bonded nAChR is less dynamic in certain domains than the apo form of the conotoxin-AChR complex. Some critical interactions in the binding site such as the salt bridge formed between K145/D200 in the neurotoxin-nAChR complex is further stabilized during the MD simulation, while it is obviously more labile in the apo form., Conclusion: These observations could support the claim that alpha neurotoxins stabilize the nAChR resting state.