Аннотация:Although the spatial structures of short-chain α-neurotoxins from snakes are known the accurate structure of the complex is not yet known. Here we present a molecular dynamics (MD) validation for the model of a short α-neurotoxin, neurotoxin II from Naja oxiana (NTII), bound to Torpedo californica muscletype nicotinic acetylcholine receptors (nAChR). It was built by comparative modeling and docking. The refinement of the constructed model was done on the basis of computer simulations. The runs were done for the system comprising α- and γ-subunits of nAChR and the toxin disposed according to the docking simulations.
During the MD calculation, all elements of secondary structure were well preserved and most of the contacts between the NTII and nAChR residues found by docking simulation were generally retained during MD operations. The toxin molecule squeezed a bit further between the subunits. The highly conserved and structurally stable cysteine-rich core of the toxin, which was initially more distant from the receptor's subunits, approached the γ-subunit, resulting in a decrease by 10° of the angle between the principal molecular axes of the toxin and receptor. MD simulation also confirmed five contacts of particular interest between residues of the receptor and NTII which seem to determine mainly their specific interaction. Further models will be applied for the rational design of new antagonists of nAChR and will be also tested by MD as the final verification tool.
