Antimicrobial peptides bind more strongly to membrane pores.
Antimicrobial peptides bind more strongly to membrane pores.
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DOI：
10.1016/j.bbamem.2010.02.023
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发表时间：
2010-08
影响因子：
3.4
通讯作者：
Lazaridis, Themis
中科院分区：
文献类型：
--
作者：
Mihajlovic, Maja;Lazaridis, Themis
关键词：
抗菌肽(AMPs)是一种小分子，通常是阳离子的多肽，可以穿透细菌的细胞膜。了解它们的作用机制可能有助于设计出更好的抗生素。使用隐式膜模型，修改后包括不同形状的孔，我们表明四种AMP(甲氨美辛、蜂毒素、一种Mainin类似物、MG-H2和鱼腥草素1)与膜孔结合更强，与它们稳定膜孔的想法一致。阿霉菌素在圆柱孔中的有效能量与在环形孔中的有效能量相似，而其他三种多肽在环形孔中的有效能量较低。只有甲氧西林插层进入膜核心，MG-H2、蜂毒素和鱼腥草素仅位于疏水/亲水界面。在环状孔道中，后三种多肽通常结合在孔边，呈斜向排列。计算的多肽结合能与它们的溶血活性相关。我们推测，AMP的一个显著特征可能是它们不完全两亲性，这使得它们能够更强地结合到环状毛孔上。对蜂毒素突变体的初步测试似乎支持这一假设。
Antimicrobial peptides (AMPs) are small, usually cationic peptides, which permeabilize bacterial membranes. Understanding their mechanism of action might help design better antibiotics. Using an implicit membrane model, modified to include pores of different shapes, we show that four AMPs (alamethicin, melittin, a magainin analogue, MG-H2, and piscidin 1) bind more strongly to membrane pores, consistent with the idea that they stabilize them. The effective energy of alamethicin in cylindrical pores is similar to that in toroidal pores, whereas the effective energy of the other three peptides is lower in toroidal pores. Only alamethicin intercalates into the membrane core; MG-H2, melittin and piscidin are located exclusively at the hydrophobic/hydrophilic interface. In toroidal pores, the latter three peptides often bind at the edge of the pore, and are in an oblique orientation. The calculated binding energies of the peptides are correlated with their hemolytic activities. We hypothesize that one distinguishing feature of AMPs may be the fact that they are imperfectly amphipathic which allows them to bind more strongly to toroidal pores. An initial test on a melittin-based mutant seems to support this hypothesis.
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