人类抗菌肽LL-37在模型POPC和POPG脂质双层中的分子动力学模拟,International Journal of Molecular Sciences

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人类抗菌肽LL-37在模型POPC和POPG脂质双层中的分子动力学模拟
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2018-04-13 , DOI: 10.3390/ijms19041186
Liling Zhao , Zanxia Cao , Yunqiang Bian , Guodong Hu , Jihua Wang , Yaoqi Zhou

鞘磷脂是在哺乳动物中发现的具有广谱抗菌活性的阳离子抗菌肽（AMPs）家族。LL-37是人Cathelicidins家族的唯一两亲性α-螺旋AMP。LL-37除具有杀菌功能外，还具有抗病毒，抗肿瘤和免疫调节活性。尽管进行了许多实验研究，但其分子作用机理尚未完全了解。在这里，我们在存在256个脂双层的情况下，使用模拟细菌和细菌的1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol（POPG），在256个脂双层存在下，对LL-37肽进行了三个独立的分子动力学模拟（600 ns或更长时间）。模仿哺乳动物膜的1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine（POPC）。我们发现LL-37可以快速吸收到POPG双层上，而不会损失其在核心区域的螺旋构象，并且螺旋平行于双层。POPG双层变形。相反，LL-37在到达POPC表面时较慢，并且在与双层相互作用期间丧失了许多螺旋构象。LL-37仅部分进入POPC双层，而膜没有明显变形。观察到的不同双层的差异主要是由于LL-37带正电，POPG带负电，POPC是中性。我们的模拟结果证明了LL-37破坏细菌膜的初始阶段的原子细节。与LL-37的实验结果进行了比较，并在其他系统中进行了仿真研究。

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Molecular Dynamics Simulations of Human Antimicrobial Peptide LL-37 in Model POPC and POPG Lipid Bilayers

Cathelicidins are a large family of cationic antimicrobial peptides (AMPs) found in mammals with broad spectrum antimicrobial activity. LL-37 is the sole amphipathic α-helical AMP from human Cathelicidins family. In addition to its bactericidal capability, LL-37 has antiviral, anti-tumor, and immunoregulatory activity. Despite many experimental studies, its molecular mechanism of action is not yet fully understood. Here, we performed three independent molecular dynamics simulations (600 ns or more) of a LL-37 peptide in the presence of 256 lipid bilayers with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) mimicking bacterial and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) mimicking mammalian membranes. We found that LL-37 can be quickly absorbed onto the POPG bilayer without loss of its helical conformation in the core region and with the helix lying in parallel to the bilayer. The POPG bilayer was deformed. In contrast, LL-37 is slower in reaching the POPC surface and loss much of its helical conformation during the interaction with the bilayer. LL-37 only partially entered the POPC bilayer without significant deformation of the membrane. The observed difference for different bilayers is largely due to the fact that LL-37 is positively charged, POPG is negatively charged, and POPC is neutral. Our simulation results demonstrated the initial stage of disruption of the bacterial membrane by LL-37 in atomic details. Comparison to experimental results on LL-37 and simulation studies in other systems was made.

更新日期：2018-04-13

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