Certain cationic peptides interact with biological membranes. These often-complex interactions can result in peptide targeting to the membrane, or in membrane permeation, rupture, and cell lysis. We investigated the relationship between the structural features of membrane-active peptides and these effects, to better understand these processes. To this end, we employed a computational method for morphing a membranolytic antimicrobial peptide into a nonmembranolytic mitochondrial targeting peptide by “directed simulated evolution.” The results obtained demonstrate that superficially subtle sequence modifications can strongly affect the peptides’ membranolytic and membrane-targeting abilities. Spectroscopic and computational analyses suggest that N- and C-terminal structural flexibility plays a crucial role in determining the mode of peptide–membrane interaction.

中文翻译：

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靶向与裂解之间的肽膜相互作用

某些阳离子肽与生物膜相互作用。这些通常复杂的相互作用可能导致肽靶向膜，或导致膜渗透，破裂和细胞裂解。我们调查了膜活性肽的结构特征与这些效应之间的关系，以更好地理解这些过程。为此，我们采用了一种计算方法，通过“定向模拟进化”将膜分解性抗菌肽转化为非膜分解性线粒体靶向肽。获得的结果表明，表面上的细微序列修饰会强烈影响肽的膜分解和膜靶向能力。