Effects of Antimicrobial Peptide Revealed by Simulations: Translocation, Pore Formation, Membrane Corrugation and Euler Buckling

Chen, Licui; Jia, Nana; Ling, Gao; Fang, Wei‐Hai; Golubović, Leonardo

doi:10.3390/ijms14047932

Cited by 16 publications

(16 citation statements)

References 27 publications

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“…However, most CG methods (such as MARTINI and DPD) with an explicit solvent are still not efficient in simulating the long-time dynamics of large vesicles. To date, only the DPD method has been used by us to simulate a small vesicle containing 1200 lipid molecules and with a radius of 7 nm and its interaction with model AMPs (28). We found that the small vesicle was ruptured by the AMPs and resealed again.…”

Section: Introductionmentioning

confidence: 92%

“…The CG MARTINI force field has been used to observe the spontaneous buckling and budding of a lipid bilayer induced by magainin 2, which were presumed to lead to very large transient pores that were larger than what was indicated by the equilibrium structures (26). We recently presented systematic CG dissipative particle dynamics (DPD) simulations of various types of antimicrobial peptides with different secondary structures interacting with a lipid bilayer membrane (27)(28)(29)(30). We found that peptides use multiple mechanisms to exert their membrane-disruptive activities, which involve stable pores, transient pores, and buckling.…”

Section: Introductionmentioning

confidence: 99%

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Peptide-Lipid Interaction Sites Affect Vesicles’ Responses to Antimicrobial Peptides

Shi

Wan

et al. 2018

Biophysical Journal

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This article presents coarse-grained molecular dynamics simulations of pore-forming antimicrobial peptide melittin and its interactions with vesicles composed of a mixture of zwitterionic and anionic phospholipids. Besides creating holes in the membrane, the adsorption of melittin also induces vesicle budding, which can develop into vesiculation at high peptide concentrations, as well as vesicle invagination, which can eventually result in a corrugated membrane surface. These rich morphology changes are mediated by the curvature of the vesicles and the peptide concentration. Highly curved vesicles favor the recruitment of melittins with a higher density of binding sites. The peptides mainly penetrate into the membrane surface in monomers via hydrophobic interaction. Lowly curved vesicles recruit melittins with a low density of binding sites. Surplus peptides are prone to form oligomers and shallowly adsorb on the surface of membrane via electrostatic interaction. The penetration of monomers induces membrane pore formation and positive membrane curvature, which promote vesicle budding. The adsorption of oligomers induces negative membrane curvature, which promotes vesicle invagination. This work demonstrates that antimicrobial peptides adopt multiple actions to destroy bacterial membranes.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Peptide-Lipid Interaction Sites Affect Vesicles’ Responses to Antimicrobial Peptides

Shi

Wan

et al. 2018

Biophysical Journal

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“…The temperature replica exchange protocol (replica-exchange MD) (40) was exploited in structural studies (41)(42)(43)(44). The dissipative particle dynamics (45), which is a variant of CG MD, was applied in a study of pore formation and other bilayer deformations caused by several different MAPs (46). Umbrella sampling with a novel reaction coordinate was used in a work on antimicrobial lipopeptides forming a micelle and fusing with a membrane (47).…”

Section: Simulation Of Membrane-active Peptidesmentioning

confidence: 99%

Structural Behavior of the Peptaibol Harzianin HK VI in a DMPC Bilayer: Insights from MD Simulations

Putzu

Kara

Afonin

et al. 2017

Biophysical Journal

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Microsecond molecular dynamics simulations of harzianin HK VI (HZ) interacting with a dimyristoylphosphatidylcholine bilayer were performed at the condition of low peptide-to-lipid ratio. Two orientations of HZ molecule in the bilayer were found and characterized. In the orientation perpendicular to the bilayer surface, HZ induces a local thinning of the bilayer. When inserted into the bilayer parallel to its surface, HZ is located nearly completely within the hydrophobic region of the bilayer. A combination of solid-state NMR and circular dichroism experiments found the latter orientation to be dominant. An extended sampling simulation provided qualitative results and showed the same orientation to be a global minimum of free energy. The secondary structure of HZ was characterized, and it was found to be located in the 3-helical family. The specific challenges of computer simulation of nonpolar peptides are discussed briefly.

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“…Most AMPs exert their activity by disrupting target microorganism membranes via the barrel‐stave model or the toroidal model. In the toroidal model, peptides insert into the membrane by forming a bundle, resulting in pore formation (Chen et al ., ). Melittin (GIGAVLKVLTTGLPALISWIKRKRQQ‐NH 2 ), the principal active component in the venom of the honeybee, Apis mellifera (Habermann, ), is a prototype toroidal pore‐forming peptide (Guilhelmelli et al ., ), and its membranolytic mechanism has been well‐established in many studies.…”

Section: Introductionmentioning

confidence: 97%

Melittin triggers apoptosis inCandida albicansthrough the reactive oxygen species-mediated mitochondria/caspase-dependent pathway

Lee

2014

FEMS Microbiol Lett

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Melittin is one of the best-studied antimicrobial peptides, and many studies have focused on the membrane underlying its membrane-disruptive activity. We previously showed that melittin could cause some hallmarks of apoptosis in Candida albicans. Here, we first report the exact mechanism of melittin-induced fungal apoptosis. We first characterized the reactive oxygen species generated by melittin. The results showed that melittin strongly produced highly reactive hydroxyl radicals (˙OH), which contribute to cell death. Next, we showed that melittin also disrupted the mitochondrial membrane potential (ΔΨm) and induced the Ca(2+) release from the endoplasmic reticulum and its remarkable accumulation in mitochondria. Finally, we investigated the role of caspase in the apoptotic pathway. The results showed that melittin activated metacaspase, which was mediated by cytochrome c release. To summarize, melittin is involved in the mitochondria- and caspase-dependent apoptotic pathway in C. albicans. Our findings suggest that melittin possesses a dual antimicrobial mechanism, including membrane-disruptive and apoptotic actions.

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Effects of Antimicrobial Peptide Revealed by Simulations: Translocation, Pore Formation, Membrane Corrugation and Euler Buckling

Cited by 16 publications

References 27 publications

Peptide-Lipid Interaction Sites Affect Vesicles’ Responses to Antimicrobial Peptides

Peptide-Lipid Interaction Sites Affect Vesicles’ Responses to Antimicrobial Peptides

Structural Behavior of the Peptaibol Harzianin HK VI in a DMPC Bilayer: Insights from MD Simulations

Melittin triggers apoptosis inCandida albicansthrough the reactive oxygen species-mediated mitochondria/caspase-dependent pathway

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