Solution structure of α-conotoxin MI determined by -NMR spectroscopy and molecular dynamics simulation with the explicit solvent water

Abstract The conformation of α-conotoxin MI, a potent antagonist of the nicotinic acetylcholine receptor, has been investigated in aqueous solution. Two-dimensional NMR experiments and simulated annealing calculations provide the overall topology of α-conotoxin MI; then molecular dynamics simulation with the explicit solvent water was followed in order to obtain a more reliable solution structure. The resulting conformation indicates the presence of a 3 10 helix and a type I β-turn for residues Pro6–Cys8 and Gly9–Try12, respectively, and shows a significant structural similarity to that of α-conotoxin GI, which has biological activity similar to that of MI. The present study provides a molecular basis for the α-conotoxin–receptor interaction.