The penetration of a charged peptide across a membrane under an external electric field: a coarse-grained molecular dynamics simulation

Wang, Bin; Zhang, Jianhua; Zhang, Youyu; Zheng, Min; Lü, Nan; Liu, Qing

doi:10.1039/c8ra07654e

Cited by 9 publications

(10 citation statements)

References 48 publications

(78 reference statements)

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“…Regardless of these differences, no simulation studies have observed the direct permeation of polyarginines, and the free energy barrier extracted for direct R 10 penetration across the 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC) bilayer was estimated from biased simulations to be a massive ∼130 kJ/mol . Other simulation studies have suggested that a potential applied across the membrane could facilitate permeation, , yet it is not directly evident how a mechanism based on a potential gradient would discriminate between polyarginines and polylysines. Still, the membrane potential seems to play a role in cells, as demonstrated by a recent experimental study highlighting the role of ion channels in generating permeable pores .…”

Section: Introductionmentioning

confidence: 99%

Ionic Strength and Solution Composition Dictate the Adsorption of Cell-Penetrating Peptides onto Phosphatidylcholine Membranes

et al. 2022

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Adsorption of arginine-rich positively charged peptides onto neutral zwitterionic phosphocholine (PC) bilayers is a key step in the translocation of those potent cell-penetrating peptides into the cell interior. In the past, we have shown both theoretically and experimentally that polyarginines adsorb to the neutral PC-supported lipid bilayers in contrast to polylysines. However, comparing our results with previous studies showed that the results often do not match even at the qualitative level. The adsorption of arginine-rich peptides onto 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPC) may qualitatively depend on the actual experimental conditions where binding experiments have been performed. In this work, we systematically studied the adsorption of R 9 and K 9 peptides onto the POPC bilayer, aided by molecular dynamics (MD) simulations and fluorescence cross-correlation spectroscopy (FCCS) experiments. Using MD simulations, we tested a series of increasing peptide concentrations, in parallel with increasing Na + and Ca 2+ salt concentrations, showing that the apparent strength of adsorption of R 9 decreases upon the increase of peptide or salt concentration in the system. The key result from the simulations is that the salt concentrations used experimentally can alter the picture of peptide adsorption qualitatively. Using FCCS experiments with fluorescently labeled R 9 and K 9 , we first demonstrated that the binding of R 9 to POPC is tighter by almost 2 orders of magnitude compared to that of K 9 . Finally, upon the addition of an excess of either Na + or Ca 2+ ions with R 9 , the total fluorescence correlation signal is lost, which implies the unbinding of R 9 from the PC bilayer, in agreement with our predictions from MD simulations.

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Section: Introductionmentioning

confidence: 99%

Ionic Strength and Solution Composition Dictate the Adsorption of Cell-Penetrating Peptides onto Phosphatidylcholine Membranes

et al. 2022

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“…Second, the external electric field was applied in all the simulations, including the WE simulations, and this electric field could contribute to the significant distortions of the membrane because our membrane has asymmetric distributions of DOPG lipids in both layers. It has been shown that the penetration of R8 within coarse-grained simulations depends on the external electric field 46 , and the authors showed that a higher electric field resulted in a short penetration time. The free energy calculations were also dependent on the electrostatic properties of the membrane 47 .…”

Section: Discussionmentioning

confidence: 99%

Translocation of a single Arg$$_9$$ peptide across a DOPC/DOPG(4:1) model membrane using the weighted ensemble method

Choe

2023

Sci Rep

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It is difficult to observe a spontaneous translocation of cell-penetrating peptides(CPPs) within a short time scale (e.g., a few hundred ns) in all-atom molecular dynamics(MD) simulations because the time required for the translocation of usual CPPs is on the order of minutes or so. In this work, we report a spontaneous translocation of a single Arg$$_9$$ 9 (R9) across a DOPC/DOPG(4:1) model membrane within an order of a few tens ns scale by using the weighted ensemble(WE) method. We identify how water molecules and the orientation of Arg$$_9$$ 9 play a role in translocation. We also show how lipid molecules are transported along with Arg$$_9$$ 9 . In addition, we present free energy profiles of the translocation across the membrane using umbrella sampling and show that a single Arg$$_9$$ 9 translocation is energetically unfavorable. We expect that the WE method can help study interactions of CPPs with various model membranes within MD simulation approaches.

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“…The application of an electric field to the system of capzip capsule-bacterial membrane accelerates the bilayer disruption process, as reported previously. 112 This is due to perturbations caused to the membraneous arrangement by the inserting peptide through charged and hydrogen bond interactions mentioned before. These promote charged arginine residue insertion and initiate water penetration in the hydrophobic core of the membrane.…”

Section: Capzip In Solutionmentioning

confidence: 98%

Nanocapsule designs for antimicrobial resistance

et al. 2021

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The penetration of a charged peptide across a membrane under an external electric field: a coarse-grained molecular dynamics simulation

Abstract: The processes of single polyarginine (R8) peptide penetration through planar and vesicle membranes under an external electric field are simulated via a coarse-grained molecular dynamics (CGMD) simulation.

Cited by 9 publications

References 48 publications

Ionic Strength and Solution Composition Dictate the Adsorption of Cell-Penetrating Peptides onto Phosphatidylcholine Membranes

Ionic Strength and Solution Composition Dictate the Adsorption of Cell-Penetrating Peptides onto Phosphatidylcholine Membranes

Translocation of a single Arg$$_9$$ peptide across a DOPC/DOPG(4:1) model membrane using the weighted ensemble method

Nanocapsule designs for antimicrobial resistance

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