Molecular dynamics study of structure and gating of low molecular weight ion channels

We implement molecular dynamics (MD) simulations on low molecular weight alpha helix-based functional synthetic and native ion channels. The synthetic channels are the LS2 proton channel and the LS3 voltage-gated channel. The simulation manifests key features of the channels such as the coiled-coil structure of the alpha-helix bundle and the continuous aqueous pore. By implementing simulations with and without an applied voltage, we develop a hypothesis as to the voltage-gating mechanism. The native channel is the M2 proton channel in the influenza A virus, which plays an essential role in the infection process. This channel is pH gated via protonation of one or more imidazole rings in the H37 residues. Simulation of the neutral channel reveals a coiled-coil structure whose pore is penetrated by water, but not threaded by a water column. By means of simulations with different numbers of charged H37 residues, we demonstrate a possible gating action via opening up the channel to a continuous water column, and also provide support for the alternative proton relay gating mechanism.