Modeling and Simulation of Bacterial Outer Membranes with Lipopolysaccharides and Enterobacterial Common Antigen
Modeling and Simulation of Bacterial Outer Membranes with Lipopolysaccharides and Enterobacterial Common Antigen
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DOI：
10.1021/acs.jpcb.0c03353
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发表时间：
2020-07-16
影响因子：
3.3
通讯作者：
Im, Wonpil
中科院分区：
文献类型：
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作者：
Gao, Ya;Lee, Jumin;Im, Wonpil
肠杆菌共同抗原(ECA)是肠杆菌科所有成员共有的一种表面糖脂。除了脂多糖(LPS)，ECA是革兰氏阴性菌外膜(OM)的重要组成部分，使OM成为有效的、选择性的屏障，阻止有毒分子的渗透。以前的建模和模拟研究仅在外层小叶中显示了含有脂多糖的OM。在这项工作中，我们首先模拟了不同的ECA分子，并将其与不同比例的内毒素以不同比例加入到对称双层膜中，并用全原子分子动力学模拟研究了模拟OM外叶的混合双层膜的性质。对每个ECA/LPS系统的动态和灵活的构象集合进行了采样。ECA(LPS)和ECA(PG)(磷脂酰甘油连接的形式)的掺入会影响双层表面的脂质堆积和ECA/LPS的分布。疏水厚度和链序参数分析表明，ECA(PG)的引入使脂多糖的酰基链更加柔韧和无序，从而增加了脂多糖的每脂表面积。计算的每种ECA/LPS的每脂面积为构建不同比例的ECA/LPS的OMS提供了一个很好的估计，这将有助于在更真实的OMS中表征它们与外膜蛋白的相互作用。
Enterobacterial common antigen (ECA) is a surface glycolipid shared by all members of the Enterobacteriaceae family. In addition to lipopolysaccharides (LPS), ECA is an important component in the outer membrane (OM) of Gram-negative bacteria, making the OM an effective, selective barrier against the permeation of toxic molecules. Previous modeling and simulation studies represented OMs exclusively with LPS in the outer leaflet. In this work, various ECA molecules were first modeled and incorporated into symmetric bilayers with LPS in different ratios, and all-atom molecular dynamics simulations were conducted to investigate the properties of the mixed bilayers mimicking OM outer leaflets. Dynamic and flexible conformational ensembles are sampled for each ECA/LPS system. Incorporation of ECA(LPS) (an LPS core-linked form) and ECA(PG) (a phosphatidylglycerol-linked form) affects lipid packing and ECA/LPS distributions on the bilayer surface. Hydrophobic thickness and chain order parameter analyses indicate that incorporation of ECA(PG) makes the acyl chains of LPS more flexible and disordered and thus increases the area per lipid of LPS. The calculated area per lipid of each ECA/LPS provides a good estimate for building more realistic OMs with different ratios of ECA/LPS, which will be useful in order to characterize their interactions with outer membrane proteins in more realistic OMs.