Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran.
Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
J Comput Aided Mol Des. 2020 Dec;34(12):1261-1273. doi: 10.1007/s10822-020-00348-4. Epub 2020 Oct 3.
Human cathelicidin LL-37 has recently attracted interest as a potential therapeutic agent, mostly because of its ability to kill a wide variety of pathogens and cancer cells. In this study, we used molecular dynamics simulation aimed to get insights that help to correlate with the antibacterial activity of previously designed LL-37 anticancer derivative (i.e. GF-17). Two independent molecular dynamics simulation involving four units of GF-17 peptide in the mixture (9:1) of 1,2-dipalmitoyl-sn-glycero-3-phosphorylethanolamine (DPPE) and 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG), and the pure DPPG lipids were performed. Various properties of membranes such as mass density distributions, area per lipid, bilayer thickness, and lateral diffusion were examined in both systems. The results showed that the thickness of the bilayer was not affected by the presence of GF-17, while the area per lipid and lateral diffusion of lipids showed an increase. Moreover, the potential of the mean force (PMF) method was used to calculate the free energy profile for transferring GF-17 from the bulk water into both kinds of membranes. It revealed that penetration of GF-17 into the DPPG membrane was more favorable than the DPPE/DPPG membrane, and there was no energy barrier for crossing through the bilayer center. Investigation of the radius of gyration (Rg) and root mean square fluctuation (RMSF) of peptides in two membranes showed that GF-17 had more compactness and rigidity in the pure DPPG system. By examining the secondary structure of GF-17 peptide, it was seen that the α-helix, and coil structures in both DPPE/DPPG and pure DPPG membranes are dominant.
人源杀菌肽 LL-37 最近因其能够杀伤多种病原体和癌细胞的能力而引起了人们的兴趣，主要是作为一种潜在的治疗剂。在这项研究中，我们使用分子动力学模拟，旨在获得有助于与先前设计的 LL-37 抗癌衍生物（即 GF-17）的抗菌活性相关的见解。涉及到两个独立的分子动力学模拟，其中包括在 DPPE（1,2-二棕榈酰-sn-甘油-3-磷酸乙醇胺）和 DPPG（1,2-二棕榈酰-sn-甘油-3-磷酸甘油）的混合物（9:1）中四个单位的 GF-17 肽的混合（9:1），以及纯 DPPG 脂质的混合。在这两个系统中，研究了各种膜的性质，如质量密度分布、脂质面积、双层厚度和侧向扩散。结果表明，双层厚度不受 GF-17 存在的影响，而脂质面积和侧向扩散增加。此外，使用平均力势能（PMF）方法计算了 GF-17 从本体水转移到两种膜的自由能分布。结果表明，GF-17 进入 DPPG 膜的穿透比 DPPE/DPPG 膜更有利，并且穿过双层中心没有能量障碍。对两种膜中肽的旋转半径（Rg）和均方根波动（RMSF）的研究表明，GF-17 在纯 DPPG 系统中更紧凑和刚性。通过检查 GF-17 肽的二级结构，发现 DPPE/DPPG 和纯 DPPG 膜中的α-螺旋和卷曲结构占主导地位。
