Interactions of GF-17 derived from LL-37 antimicrobial peptide with bacterial membranes: a molecular dynamics simulation study.
J Comput Aided Mol Des
; 34(12): 1261-1273, 2020 12.
Article
em En
| MEDLINE
| ID: mdl-33009624
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 (91) 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilgliceróis
/
Membrana Celular
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Peptídeos Catiônicos Antimicrobianos
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Bicamadas Lipídicas
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Lipídeos de Membrana
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Antibacterianos
Limite:
Humans
Idioma:
En
Revista:
J Comput Aided Mol Des
Assunto da revista:
BIOLOGIA MOLECULAR
/
ENGENHARIA BIOMEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Irã