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Molecular dynamics simulation of the antiamoebin ion channel: linking structure and conductance.

ABSTRACT: Molecular-dynamics simulations were carried out to ascertain which of the potential multimeric forms of the transmembrane peptaibol channel, antiamoebin, is consistent with its measured conductance. Estimates of the conductance obtained through counting ions that cross the channel and by solving the Nernst-Planck equation yield consistent results, indicating that the motion of ions inside the channel can be satisfactorily described as diffusive. The calculated conductance of octameric channels is markedly higher than the conductance measured in single channel recordings, whereas the tetramer appears to be nonconducting. The conductance of the hexamer was estimated to be 115 ± 34 pS and 74 ± 20 pS, at 150 mV and 75 mV, respectively, in satisfactory agreement with the value of 90 pS measured at 75 mV. On this basis, we propose that the antiamoebin channel consists of six monomers. Its pore is large enough to accommodate K? and Cl? with their first solvation shells intact. The free energy barrier encountered by K? is only 2.2 kcal/mol whereas Cl? encounters a substantially higher barrier of nearly 5 kcal/mol. This difference makes the channel selective for cations. Ion crossing events are shown to be uncorrelated and follow Poisson statistics.

SUBMITTER: Wilson MA

PROVIDER: S-EPMC3093558 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Molecular dynamics simulation of the antiamoebin ion channel: linking structure and conductance.

Wilson Michael A MA Wei Chenyu C Bjelkmar Pär P Wallace B A BA Pohorille Andrew A

Biophysical journal 20110501 10

Molecular-dynamics simulations were carried out to ascertain which of the potential multimeric forms of the transmembrane peptaibol channel, antiamoebin, is consistent with its measured conductance. Estimates of the conductance obtained through counting ions that cross the channel and by solving the Nernst-Planck equation yield consistent results, indicating that the motion of ions inside the channel can be satisfactorily described as diffusive. The calculated conductance of octameric channels i ...[more]

PMID: 21575573

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Project description:Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how transitions occur in membrane proteins-not to mention numerous applications in drug design. Here, we present a full 1 micros atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements, including up to 120 degrees rotation of the S4 segment, changes in hydrogen-bonding patterns, but only low amounts of translation. A smaller rotation ( approximately 35 degrees ) of the extracellular end of all S4 segments is present also in a reference 0.5 micros simulation without applied field, which indicates that the crystal structure might be slightly different from the natural state of the voltage sensor. The conformation change upon hyperpolarization is closely coupled to an increase in 3(10) helix contents in S4, starting from the intracellular side. This could support a model for transition from the crystal structure where the hyperpolarization destabilizes S4-lipid hydrogen bonds, which leads to the helix rotating to keep the arginine side chains away from the hydrophobic phase, and the driving force for final relaxation by downward translation is partly entropic, which would explain the slow process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5-1 micros). Together with lipids binding in matching positions and significant thinning of the membrane also observed in experiments, this provides additional support for the predictive power of microsecond-scale membrane protein simulations.

Dataset Information

Molecular dynamics simulation of the antiamoebin ion channel: linking structure and conductance.

Publications

Molecular dynamics simulation of the antiamoebin ion channel: linking structure and conductance.

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