Key result
Molecular dynamics simulation of the ClC-ec1 protein showed that Cl- transport velocity depends on the narrowest channel region width, and mutation of E148 produces positive potential beneficial for transport.
Computational modeling of the ClC-ec1 chloride channel reveals that Cl- transport velocity is dependent on channel width and that the E148 mutation facilitates transport by altering electrostatic potential.
Does not inform clinical practice; leaves open whether E148 or channel-width modulation can be targeted in human ClC channelopathies.
In order to illustrate the ion transport mechanism of chloride channel (ClC) protein, a type of ClC protein, ClC-ec1, from Escherichia coli is embedded into an explicit membranewater system by using software VMD. Then a parallel molecular dynamics (MD) simulation is employed to equilibrate the ClC-ec1 structure for 27.5 ns at temperature 298.15 K. Based on this equilibrated structure, we compute the channel geometric size variation and electrostatic potential distribution along the channel. Meanwhile, Cl - transport process is simulated using oriented random walk method under variable external potential. The simulation result shows that Cl - transport velocity depends on the width of the narrowest channel region. Mutation of negative glutamate E148 can produce positive potential, which is beneficial for Cl - transport, around external Cl - binding region in the channel. The simulated current-voltage curves about Cl - transporting in ClC-ec1 protein agree with Jayaram’s experimental results.
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Yu et al. (2016) studied this question. Molecular dynamics simulation was evaluated on Cl- transport velocity and current-voltage curves. Molecular dynamics simulation of the ClC-ec1 protein showed that Cl- transport velocity depends on the narrowest channel region width, and mutation of E148 produces positive potential beneficial for transport.
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