Coupling Molecular Dynamics Simulations with Experiments for the Rational Design of Indolicidin-Analogous Antimicrobial Peptides

Tsai, Chen‐An; Hsu, Nan‐Jung; Wang, Chang Hsu; Lu, Chun-An; Chang, Yung; Tsai, Hui Lien; Ruaan, Rouh Chyu

doi:10.1016/j.jmb.2009.06.071

Cited by 58 publications

(33 citation statements)

References 59 publications

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“…The trajectories of the final 75 ns simulation were used for statistical analysis. All analyses were performed by our in-house program, Pine-MD, which had been employed in previous MD studies of lipid bilayers [31], amyloidogenic peptides [32,33], and antimicrobial peptides [34]. Several structural and dynamics properties of lipid bilayers were calculated.…”

Section: Methodsmentioning

confidence: 99%

A Molecular Dynamics Study of the Structural and Dynamical Properties of Putative Arsenic Substituted Lipid Bilayers

Tsai

Lee

Huang

et al. 2013

IJMS

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Cell membranes are composed mainly of phospholipids which are in turn, composed of five major chemical elements: carbon, hydrogen, nitrogen, oxygen, and phosphorus. Recent studies have suggested the possibility of sustaining life if the phosphorus is substituted by arsenic. Although this issue is still controversial, it is of interest to investigate the properties of arsenated-lipid bilayers to evaluate this possibility. In this study, we simulated arsenated-lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-arsenocholine (POAC), lipid bilayers using all-atom molecular dynamics to understand basic structural and dynamical properties, in particular, the differences from analogous 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, (POPC) lipid bilayers. Our simulations showed that POAC lipid bilayers have distinct structural and dynamical properties from those of native POPC lipid bilayers. Relative to POPC lipid bilayers, POAC lipid bilayers have a more compact structure with smaller lateral areas and greater order. The compact structure of POAC lipid bilayers is due to the fact that more inter-lipid salt bridges are formed with arsenate-choline compared to the phosphate-choline of POPC lipid bilayers. These inter-lipid salt bridges bind POAC lipids together and also slow down the head group rotation and lateral diffusion of POAC lipids. Thus, it would be anticipated that POAC and POPC lipid bilayers would have different biological implications.

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Section: Methodsmentioning

confidence: 99%

A Molecular Dynamics Study of the Structural and Dynamical Properties of Putative Arsenic Substituted Lipid Bilayers

Tsai

Lee

Huang

et al. 2013

IJMS

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“…111 Using molecular dynamics simulations, Tsai et al sought to better understand the molecular interactions between indolicidin and hypothetical erythrocyte/bacterial membranes. 109 The simulations revealed that indolicidin perturbs both membranes, but by different mechanisms. Disruption of the hypothetical erythrocyte membrane was largely due to insertion of the peptide in to the lipid bilayer and the formation of key hydrophobic contacts.…”

Section: Antimicrobial Peptidesmentioning

confidence: 98%

Synthetic Biology of Antimicrobial Discovery

Zakeri

2012

ACS Synth. Biol.

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Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

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“…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 [275]. The atomistic level of detail afforded by simulations opens the path toward the design of novel peptide analogs with increased efficacy [276].…”

Section: Computer Simulationsmentioning

confidence: 99%

Membrane Active Peptides and Their Biophysical Characterization

Avcı

Akbulut

Özkırımlı

2018

Preprint

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In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which 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. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide-membrane interaction at various levels of detail. 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. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided 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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Coupling Molecular Dynamics Simulations with Experiments for the Rational Design of Indolicidin-Analogous Antimicrobial Peptides

Cited by 58 publications

References 59 publications

A Molecular Dynamics Study of the Structural and Dynamical Properties of Putative Arsenic Substituted Lipid Bilayers

A Molecular Dynamics Study of the Structural and Dynamical Properties of Putative Arsenic Substituted Lipid Bilayers

Synthetic Biology of Antimicrobial Discovery

Membrane Active Peptides and Their Biophysical Characterization

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