A hierarchical approach for predicting the transport properties of the gramicidin A channel

Wang, Zheng; Fried, Joel

doi:10.1039/b700125h

Cited by 6 publications

(5 citation statements)

References 35 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These amine- and azide-containing building blocks can be used to rapidly generate stable, C-terminally modified derivatives of gA that retain single channel conductance properties, and can, therefore, serve as an enabling tool for basic and applied studies on ion channels. For instance, these gA-based building blocks make it possible to tune the chemical and physical properties at the opening of the pore, which is useful for basic biophysical studies of ion channels on the single molecule level ,,,– . These synthetic methods also make it possible to rapidly gain access to derivatives of gA for sensing applications, where changes in the ion flux through gA derivatives in response to a specific external stimulus can be detected using ion channel conductance measurements ,,,,,, .…”

Section: Resultsmentioning

confidence: 99%

Chemically Reactive Derivatives of Gramicidin A for Developing Ion Channel-Based Nanoprobes

et al. 2008

View full text Add to dashboard Cite

Ion channel-forming peptides and proteins offer tremendous opportunities for fundamental and applied studies of function on individual molecules. An ongoing challenge in ion channel research is the lack of simple and accessible synthetic methods to engineer pores with tailored chemical and physical properties. This paper describes a practical synthetic route to rapidly generate C-terminally modified derivatives of gramicidin A (gA), an ion channel-forming peptide, through the use of two chemically reactive gA-based building blocks. These amine- and azide-containing building blocks can react readily with typical substrates for amidation and 1,3-dipolar cycloaddition ("click") reactions to present molecules with desired structure and functionality near the opening of a gA pore. These derivatives of gA are stable under typical aqueous conditions for ion channel recordings and retain characteristic single ion channel conductance properties in planar lipid bilayers. Additionally, the synthetic methods described here afford useful quantities of these gA derivatives in good purity and yield with minimal purification. We demonstrate that derivatives of gA can be used for studying, in situ, a change in conductance through a channel upon performing a "click" reaction on an azide moiety attached to the gA pore. We also demonstrate that these gA-based building blocks can be used to construct sensors for the recognition of specific protein-ligand binding interactions in solution. This widely accessible, enabling synthetic methodology represents a powerful new tool to study relationships between chemical structure and function on the single molecule level.

show abstract

Section: Resultsmentioning

confidence: 99%

Chemically Reactive Derivatives of Gramicidin A for Developing Ion Channel-Based Nanoprobes

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Simulations have also been used to study other synthetic and biological ion channels. 4,8,37,41,44,[83][84][85][86][87][88][89][90][91][92][93][94] One method that may be useful in providing further insight into the SCMTR class of compounds is the hybrid coarse-grained/atomistic molecular dynamics used to study the channel-forming ability of antimicrobial peptides. 91 Coarse-grained dynamics were used to model the peptide's insertion process into the membrane; once inserted, the coarsegrained beads were converted to a fully atomistic representation for a more accurate investigation into pore dynamics.…”

Section: Electric Eld Simulationmentioning

confidence: 99%

The water-channel forming ability of heptapeptide-based anion channels: insights from molecular dynamics simulations

2013

View full text Add to dashboard Cite

“…The conductance of gA may be further reduced by interference with ion flow at the mouth of the ion channel by chains of PMOXA as was demonstrated for block copolymers of ethyl ethylene and ethylene oxide via coarsegraining simulations. 33 Additionally, surface charges on biological membranes, e.g., zwitterions in phosphocholine, have been shown to have an impact on the conductance of gA. 61 The polymers in this work have no such surface charge, a property that might also be implicated in differences in protein incorporation from aqueous electrolyte. The slower dynamics for state switching in the alamethicin and (in the case of gramicidin) nearly zero state switching are likely, in part, related to the lower diffusion constant in polymers.…”

Section: ■ Conclusionmentioning

confidence: 91%

Planar Bilayer Measurements of Alamethicin and Gramicidin Reconstituted in Biomimetic Block Copolymers

2017

View full text Add to dashboard Cite

This work explores methods for forming and characterizing biomimetic planar membranes composed of amphiphilic block copolymers. The membranes are diblocks and triblocks with hydrophilic blocks of poly(2-methyl-2-oxazoline) (PMOXA) and hydrophobic blocks of poly(dimethylsiloxane) (PDMS). Experiments with the lipid diphytanoyl phosphocholine (DPhPC) serve as a basis for comparison with the polymeric membranes. Phase-contrast microscopy is used to study how membranes evolve over time after their formation. Capacitance measurements as a function of the thinned membrane area (prepared from two separate solvent systems) are performed to clarify the importance of the Plateau-Gibbs border in electrical measurements. Finally, functional reconstitution of the two ion channels, alamethicin and gramicidin, is investigated. Imaging in transmitted phase-contrast mode provides visualization of thinned regions that contain monolayers or bilayers (in the case of diblock copolymer). The specific capacitance measurements yield 0.28 μF/cm with a corresponding thickness of 8.5 nm for PMOXA-PDMS-PMOXA (blocks of 6 PMOXA and 35 PDMS repeat units) formed from a solution of ethanol-decane, 0.55 μF/cm and 4.4 nm in chloroform-toluene, and 0.46 μF/cm and 5.4 nm for the diblock PMOXA-PDMS in ethanol-decane. Alamethicin reconstitution in the block copolymers shows slower channel-forming kinetics with somewhat higher conductance values than found in DPhPC. Gramicidin in the block copolymer shows a slightly voltage-dependent conductance as a function of time, with little stochastic conductance state switching, in contrast to reconstitution in DPhPC where gramicidin switches states at ∼3 Hz.

show abstract

A hierarchical approach for predicting the transport properties of the gramicidin A channel

Cited by 6 publications

References 35 publications

Chemically Reactive Derivatives of Gramicidin A for Developing Ion Channel-Based Nanoprobes

Chemically Reactive Derivatives of Gramicidin A for Developing Ion Channel-Based Nanoprobes

The water-channel forming ability of heptapeptide-based anion channels: insights from molecular dynamics simulations

Planar Bilayer Measurements of Alamethicin and Gramicidin Reconstituted in Biomimetic Block Copolymers

Contact Info

Product

Resources

About