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The common structural features of membrane-active peptides involve the adoption of a stable secondary structure upon binding to the membrane surface. The induction of a cationic amphipathic α-elical structure has been well-characterized and plays an essential role in the membrane perturbing activities of antimicrobial peptides. In contrast, similar structure−activity relationships are less well-studied for membrane-active peptides and proteins that adopt a β-sheet structure upon membrane association, although β-sheet antimicrobial peptides such as the defensins and protegrins have been wellcharacterized. Since these models all involve the binding of peptides to the membrane, the determination of the relative affinity of the peptides for a particular target membrane is central to the delineation of the mechanism of action of these peptides.