Jefferies Damien, Hsu Pin-Chia, Khalid Syma
School of Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
Biochemistry. 2017 Mar 21;56(11):1672-1679. doi: 10.1021/acs.biochem.6b01063. Epub 2017 Mar 7.
In the following, molecular simulations are used to reveal unexpected behavior within bacterial membranes. We show that lipopolysaccharide molecules found in these membranes form viscous amorphous solids when they are interlinked with monovalent and divalent cations. The bilayers exhibit both liquid and glassy characteristics, due to the coexistence of both liquid and crystalline domains in the bilayer. Polymyxin B1, a potent antimicrobial peptide, is shown to increase order within the lipopolysaccharide bilayers by inducing the formation of crystalline patches. Crucially we are able to decompose the energetics of insertion into their enthalpic and entropic components. The present coarse-grain molecular dynamics study provides unprecedented insights into the antibacterial action of antimicrobial peptides, thus paving the way for development of novel therapeutic agents to treat multiple drug resistant Gram-negative bacteria.
在接下来的内容中，分子模拟被用于揭示细菌膜内意想不到的行为。我们发现，这些膜中存在的脂多糖分子在与单价和二价阳离子相互连接时会形成粘性无定形固体。由于双层膜中同时存在液相和晶相区域，所以双层膜兼具液体和玻璃态的特性。多粘菌素B1是一种有效的抗菌肽，它通过诱导形成结晶斑块来增加脂多糖双层膜内的有序性。至关重要的是，我们能够将插入的能量学分解为焓和熵分量。目前的粗粒度分子动力学研究为抗菌肽的抗菌作用提供了前所未有的见解，从而为开发治疗多重耐药革兰氏阴性菌的新型治疗药物铺平了道路。
