Conducting-State Properties of the KcsA Potassium Channel from Molecular and Brownian Dynamics Simulations

The mechanisms underlying transport of ions across the potassium channel are examined using electrostatic calculations and three-dimensional Brownian dynamics simulations. We first build open-state configurations of the channel with molecular dynamics simulations, by pulling the transmembrane helice...

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Bibliographic Details
Published in:Biophysical journal 2002-02, Vol.82 (2), p.628-645
Main Authors: Chung, Shin-Ho, Allen, Toby W., Kuyucak, Serdar
Format: Article
Language:English
Subjects:
Bacterial Proteins
Biophysical Phenomena
Biophysics
Cell Membrane - metabolism
Computer Simulation
Dose-Response Relationship, Drug
Electric Conductivity
Hydrogen-Ion Concentration
Ions
Models, Molecular
Permeability
Potassium
Potassium - metabolism
Potassium Channels - chemistry
Potassium Channels - metabolism
Protein Conformation
Time Factors
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Summary:The mechanisms underlying transport of ions across the potassium channel are examined using electrostatic calculations and three-dimensional Brownian dynamics simulations. We first build open-state configurations of the channel with molecular dynamics simulations, by pulling the transmembrane helices outward until the channel attains the desired interior radius. To gain insights into ion permeation, we construct potential energy profiles experienced by an ion traversing the channel in the presence of other resident ions. These profiles reveal that in the absence of an applied field the channel accommodates three potassium ions in a stable equilibrium, two in the selectivity filter and one in the central cavity. In the presence of a driving potential, this three-ion state becomes unstable, and ion permeation across the channel is observed. These qualitative explanations are confirmed by the results of three-dimensional Brownian dynamics simulations. We find that the channel conducts when the ionizable residues near the extracellular entrance are fully charged and those near the intracellular side are partially charged. The conductance increases steeply as the radius of the intracellular mouth of the channel is increased from 2 Å to 5 Å. Our simulation results reproduce several experimental observations, including the current-voltage curves, conductance-concentration relationships, and outward rectification of currents.
ISSN:0006-3495
1542-0086
DOI:10.1016/S0006-3495(02)75427-1