Simulations of transmembrane channels

A major issue in computational studies of ion channels is the nature of the amphiphilic interactions between helices that allow the channel to form. We have previously discussed the affinity of amphipathic peptides for the water-membrane interface. While a degree of amphiphilicity seems to be a necessary 

The structure and stability of several other channels have also been addressed in computer simulations. In a recent study of the HIV-Vpu transmembrane domain in a water-octane system [84], the calculations were started in a pentameric, coiled-coil bundle that had been suggested as the equilibrium structure, based on simulations of the bundle with water-caps and restraining forces [125]. After initial equilibration periods of 0.5-1.5 ns, the bundle evolved into a conical structure that resembled the K+ channel [117]. This structural rearrangement had a significant effect on the channel region while the initial coiled-coil contained a continuous column of water, most of the water was expelled from the conical structure breaking a continuous water path across the channel. Similar slow relaxation times were seen in simulations of tetrameric bundles of LS3 channels in a water-octane membrane-mimetic system [82], These simulations were started 

In general, atomic-level computer simulations of channels in membranes or membrane-mimetic systems have proven to be quite useful in refining model structures, often postulated somewhat ad hoc. However, full assessments of channel stability from simulations on the currently accessible timescales is not nearly as reliable. Owing to the long relaxation times required to equilibrate membrane-bound systems, it is not currently feasible to arrive at the correct, equilibrium structure starting from an arbitrary initial conditions. Even if the potential energy functions used in simulations were accurate, correct results could be expected only if the initial and equilibrium structures were not too different. 

So far, we have focused on the structure of ion channels. Probably of even greater interest are the mechanisms by which they transport ions in a selective and controlled fashion. The gramicidin A channel transports water with 

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