Using atomistic molecular dynamics simulations, we study the interaction of ternary methacrylate polymers, composed of charged cationic, hydrophobic and neutral polar groups, with model bacterial membrane. Our simulation data shows that the random ternary polymers can penetrate deep into the membrane interior and partitioning of even a single polymer has a pronounced effect on the membrane structure. Lipid reorganization, on polymer binding, shows a strong affinity of the ternary polymer for anionic POPG lipids and the same is compared with the control case of binary polymers (only cationic and hydrophobic groups). While binary polymers exhibit strong propensity of acquired amphiphilic conformations upon membrane insertion, our results strongly suggest that such amphiphilic conformations are absent in the case of random ternary polymers. The ternary polymers adopt a more folded conformation, staying aligned in the direction of the membrane normal and subsequently penetrating deeper into the membrane interior suggesting a novel membrane partitioning mechanism without amphiphilic conformations. Finally, we also examine the interactions of ternary polymer aggregates with model bacterial membranes, which show that replacing some of the hydrophobic groups by polar groups leads to weakly held ternary aggregates enabling them to undergo rapid partitioning and insertion into membrane interior. Our work thus underscores the role of inclusion of polar groups into the framework of traditional binary biomimetic antimicrobial polymers and suggests different mode of partitioning into bacterial membranes, mimicking antimicrobial mechanism of globular antimicrobial peptides like Defensin.

中文翻译：

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设计球形抗菌肽模拟物：极性官能团在仿生三元抗菌聚合物中的作用

使用原子分子动力学模拟，我们研究了由带电荷的阳离子，疏水和中性极性基团组成的甲基丙烯酸三元共聚物与细菌膜的相互作用。我们的模拟数据表明，无规三元聚合物可以深入渗透到膜内部，即使是单一聚合物的分配也对膜结构有显着影响。脂质重组在聚合物结合后显示出三元聚合物对阴离子POPG脂质具有很强的亲和力，并且与二元聚合物的对照情况（仅阳离子和疏水基团）进行了比较。尽管二元聚合物在膜插入后表现出很强的获得性两亲构象的倾向，但我们的结果强烈表明，在无规三元聚合物的情况下，这种两亲构象是不存在的。三元聚合物采用更折叠的构象，在膜法线方向上保持排列，然后更深地渗透到膜内部，这表明没有两亲构象的新型膜分配机制。最后，我们还研究了三元聚合物聚集体与模型细菌膜的相互作用，结果表明，用极性基团取代某些疏水基团会导致三元聚集体保持不牢固，从而使它们能够快速分配并插入膜内部。因此，我们的工作强调了将极性基团包含在传统的二元仿生抗菌聚合物框架中的作用，并提出了不同的分配进入细菌膜的方式，模仿了球状抗菌肽（如防御素）的抗菌机制。