Interactions of GF-17 derived from LL-37 antimicrobial peptide with bacterial membranes: a molecular dynamics simulation
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Interactions of GF-17 derived from LL-37 antimicrobial peptide with bacterial membranes: a molecular dynamics simulation study Hossein Aghazadeh1,2 · Mokhtar Ganjali Koli2 · Reza Ranjbar3 · Kamran Pooshang Bagheri2 Received: 11 February 2020 / Accepted: 29 September 2020 © Springer Nature Switzerland AG 2020
Abstract 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-dipalmitoylsn-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. Keywords Lipid bilayer · Antimicrobial peptides · Cathelicidin LL-37 · Molecular dynamics simulation · Potential of mean force · GF-17
Introduction The increasing emergence of antibiotic resistance among human pathogens has led to the search for alternatives to overcome this alarming problem [1]. Among the very few Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10822-020-00348-4) contains supplementary material, which is available to authorized users. * Mokhtar Ganjali Koli [email protected] 1
Medical Biotechnology Research Center, Ashkezar Branch, Islamic Azad University, Ashkezar, Yazd, Iran
2
Venom and Biotherapeutics Molecules Lab, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
3
Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
novel anti-infective agents in the pipeline, antimicrobial peptides (AMPs) are promising new and effective antibio
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