Androctonin, a novel antimicrobial peptide from scorpion Androctonus australis: Solution structure and molecular dynamics simulations in the presenceof a lipid monolayer

Androctonin is a highly cationic antimicrobial peptide from scorpion exhibi ting a broad spectrum of activities against bacteria and fungi. It contains 25 amino acids including four cysteine residues forming two disulfide brid ges. We report here on the determination of its solution structure by conve ntional two-dimensional (2D) H-1-NMR spectroscopy and molecular modelling u sing distance geometry and molecular dynamics methods. The structure of and roctonin involves a well-defined highly twisted anti-parallel beta-sheet wi th strands connected by a more variable positively charged turn. A comparis on with the structure of tachyplesin I (horseshoe crab) reveals that the am phiphilic character of the protein surface of this homologous peptide is no t observed in androctonin. We have undertaken a 200-ps molecular dynamics s imulation study on a system including one androctonin molecule and a monola yer of DMPG (1,2-dimyristoylphosphatidylglycerol) lipids. On the basis of t his simulation, the first steps of the membrane permeabilization process ar e discussed.