Study of Orientation and Penetration of LAH4 into Lipid Bilayer Membranes: pH and Composition Dependence

Islami, Mohammad Reza; Mehrnejad, Faramarz; Doustdar, Farahnoosh; Alimohammadi, Masumeh; Khadem-Maaref, Mahmoud; Mir-Derikvand, Mohammad; Taghdir, Majid

doi:10.1111/cbdd.12311

Cited by 11 publications

(6 citation statements)

References 51 publications

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“…We refer to the hydrophobic interactions as the secondary interactions along the electrostatic ones, in accordance with previous results proposed by Wang et al 23,24,45 as well as similar MD studies stating the importance of electrostatic interactions in immediate peptide-membrane binding and hydrophobic interactions in subsequent insertion. 32,[47][48][49] As indicated in Figure 7A, the polar energies in the case of S. aureus were markedly stronger than that of E. coli because the existing a large number of PG lipid molecules in the S. aureus model membrane. Therefore, this composition of the membrane has the higher net charge and causes the peptide to adsorb strongly on the S. aureus model membrane.…”

Section: Density Distributions Of All Atoms In the Model Membranesmentioning

confidence: 90%

Molecular insights into the interactions of GF‐17 with the gram‐negative and gram‐positive bacterial lipid bilayers

Jahangiri

Jafari

Arjomand

et al. 2018

J of Cellular Biochemistry

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The cationic antimicrobial peptide GF-17, a 17-mer-derived peptide from human cathelicidin LL-37, has a significant strength in the killing of the methicillin-resistant Staphylococcus aureus and Escherichia coli strains. Herein, we conducted a series of all-atom molecular dynamics simulations to investigate the ability of GF-17 in perturbing the model membranes of the gram-positive, S. aureus, and gram-negative, E. coli, bacteria. We also explored the contributions of the specific residues in the peptide activity. The molecular dynamics results indicated that the peptide is stabilized on the membrane surface and rapidly binds to the phosphate headgroups of the model membranes through the electrostatic interactions and hydrogen bonds. Furthermore, both polar and nonpolar interactions are energetically favored for the binding with the membrane surface. The research also revealed the important roles of the phenylalanine residues in the early insertion of the peptide into the bacterial model membranes. In addition, the results demonstrated that the central residues Arg23 and Lys25 played a critical role in the binding of GF-17 to both gram-negative and gram-positive model membranes, in excellent agreement with experimental studies. This study emphasizes on the pivotal role of basic residues in prompt association of the peptide on the model membrane surface and on the significance of residues Phe17, Ile24, Phe27, and Val32 in hydrophobic interactions. Therefore, our observations provide insights into the membrane-GF-17 interactions at atomic details that are useful to develop potent antimicrobial peptides targeting multidrug-resistant bacteria.

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Section: Density Distributions Of All Atoms In the Model Membranesmentioning

confidence: 90%

Molecular insights into the interactions of GF‐17 with the gram‐negative and gram‐positive bacterial lipid bilayers

Jahangiri

Jafari

Arjomand

et al. 2018

J of Cellular Biochemistry

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“…They can also provide valuable information on the mechanism of peptide–lipid interaction toward differentiating between different working models [ 41 ]. Simulations can also shed light on the mechanism of selectivity against bacterial or mammalian cell membranes, giving details on the type of interactions and weak contacts (e.g., hydrogen and van der Waals) that drive the process forward [ 291 , 292 ]. Computational approaches can further give an insight to the initial electrostatic interactions that govern the binding of lipopeptides to the hydrophobic core of the membrane [ 293 ].…”

Section: Computer Simulationsmentioning

confidence: 99%

Membrane Active Peptides and Their Biophysical Characterization

2018

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In the last 20 years, an increasing number of studies have been reported on membrane active peptides. These peptides exert their biological activity by interacting with the cell membrane, either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. Membrane active peptides are attractive alternatives to currently used pharmaceuticals and the number of antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery in the drug pipeline is increasing. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). Antimicrobial peptides are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus, and fungi. Cell penetrating peptides are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity. Biophysical techniques shed light on peptide–membrane interactions at higher resolution due to the advances in optics, image processing, and computational resources. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Live imaging techniques allow examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provide clues on the peptide–lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

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“…AMPs kill bacteria using different mechanisms of action, including disruption of the lipid bilayer, interference with cellular metabolism, and targeting of cytoplasmic signaling pathways. , The mechanism behind these activities is not exactly understood yet, although it has been suggested that the membrane-active mechanism of AMPs has the most potential to overcome or alleviate cellular resistance . Experimentally, the study of the biological membrane model in atomic detail is difficult. , With the increasing availability of computing resources, molecular dynamics (MD) simulations can provide valuable data about the various stages of protein–membrane interactions at an atomic level. − MD simulations of peptides and proteins in lipid bilayer models enable modeling of the dynamics and functional properties, and they also facilitate investigations of lipid and protein interactions at atomic detail …”

Section: Introductionmentioning

confidence: 99%

Identification of the Crucial Residues in the Early Insertion of Pardaxin into Different Phospholipid Bilayers

Jafari

Mehrnejad

Aghdami

et al. 2017

J. Chem. Inf. Model.

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Antimicrobial peptides (AMPs) are part of the innate host defense system, and they are produced by living organisms to defend themselves against infections. Pardaxin is a cationic AMP with antimicrobial and antitumor activities that has potential to be used as a novel antibiotic or for drug delivery in cancer therapy. This peptide acts on the membrane of target cells and can lead to lysis using different mechanisms of action. Here, we conducted 4.5 μs all-atom molecular dynamics (MD) simulations to determine the critical fragments and residues of Pardaxin for early insertion into different lipid bilayers. Our results revealed that the N-terminal domain of the peptide, particularly the Phe 2 and (/or) Phe 3 residues, has a crucial role in early insertion, independent of the type of lipid bilayers.

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Study of Orientation and Penetration of LAH4 into Lipid Bilayer Membranes: pH and Composition Dependence

Cited by 11 publications

References 51 publications

Molecular insights into the interactions of GF‐17 with the gram‐negative and gram‐positive bacterial lipid bilayers

Molecular insights into the interactions of GF‐17 with the gram‐negative and gram‐positive bacterial lipid bilayers

Membrane Active Peptides and Their Biophysical Characterization

Identification of the Crucial Residues in the Early Insertion of Pardaxin into Different Phospholipid Bilayers

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