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

We implement molecular dynamics (MD) simulations on low molecular weight al pha 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 port. By imp lementing simulations with and without an applied voltage, we develop a hyp othesis as to the voltage-gating mechanism. The native channel is the M2 pr oton 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 rev eals a coiled-coil structure whose pore is penetrated by water, but not thr eaded by a water column. By means of simulations with different numbers of charged H37 residues, we demonstrate a possible gating action via opening u p the channel to a continuous water column, and also provide support for th e alternative proton relay gating mechanism. (C) 2000 Published by Elsevier Science B.V. All rights reserved.