Antimicrobial Peptide Potency is Facilitated by Greater Conformational Flexibility when Binding to Gram-negative Bacterial Inner Membranes.
Antimicrobial Peptide Potency is Facilitated by Greater Conformational Flexibility when Binding to Gram-negative Bacterial Inner Membranes.
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DOI：
10.1038/srep37639
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发表时间：
2016-11-22
影响因子：
4.6
通讯作者：
Mason AJ
中科院分区：
文献类型：
--
作者：
Amos ST;Vermeer LS;Ferguson PM;Kozlowska J;Davy M;Bui TT;Drake AF;Lorenz CD;Mason AJ
抗菌肽（AMPs）与革兰氏阴性菌内膜的相互作用是其发挥多种杀菌作用的关键决定因素。在这里，我们提出了两个阳离子α-螺旋AMPs的初始目标膜相互作用的分子水平的理解，它们具有结构相似性，但对革兰氏阴性细菌的抗菌效力相差10倍。在所有原子分子动力学模拟中，在100 ns内监测了由128个阴离子脂质和384个两性离子脂质组成的革兰氏阴性菌的内膜与乳酸菌或乳酸菌2溶液的结合和插入。考虑了膜相互作用对肽和脂质成分的影响，并与在稳态下获得的新的和已发表的实验数据进行了比较。虽然乳酸菌素2和乳酸菌素都能够破坏细菌膜，但乳酸菌素的更大效力与其穿透细菌细胞的能力有关。我们发现，与magainin 2相比，乳酸菌素表现出更大的构象灵活性，在膜表面抵抗自结合，并进一步渗透到脂质双分子层的疏水核心。因此，构象柔韧性是明显α-螺旋阳离子AMPs增强抗菌效力所需的关键特征。
The interaction of antimicrobial peptides (AMPs) with the inner membrane of Gram-negative bacteria is a key determinant of their abilities to exert diverse bactericidal effects. Here we present a molecular level understanding of the initial target membrane interaction for two cationic α-helical AMPs that share structural similarities but have a ten-fold difference in antibacterial potency towards Gram-negative bacteria. The binding and insertion from solution of pleurocidin or magainin 2 to membranes representing the inner membrane of Gram-negative bacteria, comprising a mixture of 128 anionic and 384 zwitterionic lipids, is monitored over 100 ns in all atom molecular dynamics simulations. The effects of the membrane interaction on both the peptide and lipid constituents are considered and compared with new and published experimental data obtained in the steady state. While both magainin 2 and pleurocidin are capable of disrupting bacterial membranes, the greater potency of pleurocidin is linked to its ability to penetrate within the bacterial cell. We show that pleurocidin displays much greater conformational flexibility when compared with magainin 2, resists self-association at the membrane surface and penetrates further into the hydrophobic core of the lipid bilayer. Conformational flexibility is therefore revealed as a key feature required of apparently α-helical cationic AMPs for enhanced antibacterial potency.
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影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
8
作者：
BECHINGER, B;ZASLOFF, M;OPELLA, SJ
通讯作者：
OPELLA, SJ
影响因子：
3.4
作者：
Gregory, Sonia M.;Pokorny, Antje;Almeida, Paulo F. F.
通讯作者：
Almeida, Paulo F. F.