Lipid A is one the three components of bacterial lipopolysaccharides constituting the outer membrane of Gram-negative bacteria, and is recognized to have an important biological role in the inflammatory response of the immune system. Its biological activity is modulated by the number of acyl-chains that are present in the lipid and by the dielectric medium, i.e., the type of counter-ions, through electrostatic interactions. In this paper, we report a coarse-grained model of poly-acyl Lipid A based on the hybrid particle field molecular dynamics approach (hPF-MD). In particular, we investigate the stability of Lipid A bilayers for two different hexa- and tetra-acylation states. Comparing particle density profiles along bilayer cross-sections, we find good agreement between our hPF-MD and reference all-atom simulation results for both bilayers. hPF-MD models of constituted bilayers composed by hexa-acylated Lipid A in water are stable within the simulation time. We further validate our model by verifying that the phase behavior of Lipid A/counterion/water mixtures is correctly reproduced. In particular, hPF-MD simulations predict the correct self-assembly of different lamellar and micellar phases from an initially random distribution of Lipid A molecules with counterions in water. Finally, it is possible to observe the spontaneous formation and stability of Lipid A vesicles by fusion of micellar aggregates.

中文翻译：

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脂质A变体的聚集：混合粒子场模型。

脂质A是构成革兰氏阴性细菌外膜的细菌脂多糖的三个成分之一，并且被认为在免疫系统的炎症反应中具有重要的生物学作用。它的生物活性通过脂质中存在的酰基链数量和介电介质（即抗衡离子的类型）通过静电相互作用来调节。在本文中，我们报告了基于杂化粒子场分子动力学方法（hPF-MD）的多聚脂类脂质A的粗粒度模型。特别是，我们研究了两种不同的六酰和四酰化态脂质A双层的稳定性。比较双层横截面的颗粒密度分布，我们发现我们的hPF-MD与两个双层参考全原子模拟结果之间都有很好的一致性。在水中由六酰化脂质A构成的双层结构的hPF-MD模型在模拟时间内是稳定的。我们通过验证脂质A /抗衡剂/水混合物的相行为是否正确再现来进一步验证模型。尤其是，hPF-MD模拟可根据脂质A分子在水中与抗衡离子的初始随机分布，预测不同层状和胶束相的正确自组装。最后，可以通过胶束聚集体的融合观察脂质A囊泡的自发形成和稳定性。hPF-MD模拟可从脂质A分子与抗衡离子在水中的初始随机分布预测不同的层状和胶束相的正确自组装。最后，可以通过胶束聚集体的融合观察脂质A囊泡的自发形成和稳定性。hPF-MD模拟可从脂质A分子与抗衡离子在水中的初始随机分布预测不同的层状和胶束相的正确自组装。最后，可以通过胶束聚集体的融合观察脂质A囊泡的自发形成和稳定性。