title: Binding of long-chain alpha-neurotoxin would stabilize the resting state of nAChR: a comparative study with alpha-conotoxin.
abstract: 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.
  
  
  CONCLUSIONS
  These observations could support the claim that alpha neurotoxins stabilize the nAChR resting state.
authors.affiliation: Department of Biophysics, Faculty of Science, Tarbiat Modares University, P,O, Box 14115-175, Tehran, Iran. nasiripour@modares.ac.ir
authors.forename: Adak
authors.initials: A
authors.lastname: Nasiripourdori
authors.forename: Bijan
authors.initials: B
authors.lastname: Ranjbar
authors.forename: Hossein
authors.initials: H
authors.lastname: Naderi-Manesh
mesh_terms: D000818:Animals; D020916:Conotoxins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D014101:Torpedo
chemical_list: D020916:Conotoxins; D009498:Neurotoxins; D011978:Receptors, Nicotinic