A thermodynamic approach to alamethicin pore formation

Abstract

The structure and energetics of alamethicin Rf30 monomer to nonamer in cylindrical pores of 5 to 11 Å radius are investigated using molecular dynamics simulations in an implicit membrane model that includes the free energy cost of acyl chain hydrophobic area exposure. Stable, low energy pores are obtained for certain combinations of radius and oligomeric number. The trimer and the tetramer formed 6 Å pores that appear closed while the larger oligomers formed open pores at their optimal radius. The hexamer in an 8 Å pore and the octamer in an 11 Å pore give the lowest effective energy per monomer. However, all oligomers beyond the pentamer have comparable energies, consistent with the observation of multiple conductance levels. The results are consistent with the widely accepted “barrel-stave” model. The N terminal portion of the molecule exhibits smaller tilt with respect to the membrane normal than the C terminal portion, resulting in a pore shape that is a hybrid between a funnel and an hourglass. Transmembrane voltage has little effect on the structure of the oligomers but enhances or decreases their stability depending on its orientation. Antiparallel bundles are lower in energy than the commonly accepted parallel ones and could be present under certain experimental conditions. Dry aggregates (without an aqueous pore) have lower average effective energy than the corresponding aggregates in a pore, suggesting that alamethicin pores may be excited states that are stabilized in part by voltage and in part by the ion flow itself.

The puzzle of metabolite exchange and identification of putative octotrico peptide repeat expression regulators in the nascent photosynthetic organelles ofPaulinella chromatophora

“…The predicted porelining residues (Table S4) in many of these proteins further suggest that they could form homo-or hetero-oligomeric channels. It has been previously reported that AMPs can arrange in channel-like assemblies which facilitate diffusion along concentration gradients (58,59), though the lifetime and selectivity of such arrangements requires further investigation. Given the size of the metabolites to be transported, they would be required to form multimer arrangements in barrel-stave ( Fig.…”

Computational studies of peptide-induced membrane pore formation

“…Implicit simulations in our laboratory that accounted for the free energy cost of acyl chain exposure showed that certain antiparallel alamethicin bundles have lower free energy than parallel ones and could be present under experimental conditions [205]. Multiple combinations of radius and oligomeric number were investigated, with all oligomeric numbers 5 -9 forming open pores at their optimal radii.…”

Isolation and Total Synthesis of Albu­peptins A–D: 11‐Residue Peptaibols from the Fungus Gliocladium album

“…[14] The amphipathic nature and helical secondary structure of these compounds allows them to form voltage-dependent ion channels into biological membranes, leading to alterations in the osmotic balance of the cell. [15][16][17] Consequently, peptaibols show a wide range the isolated peptaibols 1-4 was unambiguously assigned by 1 H NMR chemical shift analysis in conjunction with solidphase peptide synthesis. By using this approach, the absolute configuration of the Iva residues in albupeptins A (1) and C (3) was determined to be D, whereas albupeptins B (2) and D (4) feature an additional Iva 5 residue with an L configuration.…”