Interactions of GF-17 derived from LL-37 antimicrobial peptide with bacterial membranes: a molecular dynamics simulation study

被引:22
作者
Aghazadeh, Hossein [1 ,2 ]
Ganjali Koli, Mokhtar [2 ]
Ranjbar, Reza [3 ]
Pooshang Bagheri, Kamran [2 ]
机构
[1] Islamic Azad Univ, Ashkezar Branch, Med Biotechnol Res Ctr, Ashkezar, Yazd, Iran
[2] Pasteur Inst Iran, Med Biotechnol Dept, Venom & Biotherapeut Mol Lab, Biotechnol Res Ctr, Tehran, Iran
[3] Baqiyatallah Univ Med Sci, Syst Biol & Poisonings Inst, Mol Biol Res Ctr, Tehran, Iran
关键词
Lipid bilayer; Antimicrobial peptides; Cathelicidin LL-37; Molecular dynamics simulation; Potential of mean force; GF-17; HUMAN CATHELICIDIN LL-37; ADDITIVE FORCE-FIELD; HONEY-BEE VENOM; MECHANISMS; DIVERSITY; BILAYERS; MELITTIN; BUILDER; BIOFILM; PV3;
D O I
10.1007/s10822-020-00348-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha-helix, and coil structures in both DPPE/DPPG and pure DPPG membranes are dominant.
引用
收藏
页码:1261 / 1273
页数:13
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