SOLUTION STRUCTURE OF ALPHA-CONOTOXIN MI DETERMINED BY H-1-NMR SPECTROSCOPY AND MOLECULAR-DYNAMICS SIMULATION WITH THE EXPLICIT SOLVENT WATER

The conformation of alpha-conotoxin MI, a potent antagonist of the nic otinic acetylcholine receptor, has been investigated in aqueous soluti on. Two-dimensional NMR experiments and simulated annealing calculatio ns provide the overall topology of alpha-conotoxin MI; then molecular dynamics simulation with the explicit solvent water was followed in or der to obtain a more reliable solution structure. The resulting confor mation indicates the presence of a 3(I0) helix and a type I beta-turn for residues Pro6-Cys8 and Gly9-Try12, respectively, and shows a signi ficant structural similarity to that of alpha-conotoxin GI, which has biological activity similar to that of MI. The present study provides a molecular basis for the alpha-conotoxin-receptor interaction. (C) 19 97 Elsevier Science B.V.