Gramicidin A is the smallest known, naturally-occurring transmembrane ion channel, and it is formed by the head-to-toe dimerization of two pentadecapeptide proteins. The peptides form a right β6.3 helix, with all the side chains pointing outwards, leaving the back bone of the protein constitute the wall of the pore. The gA has an inside diameter of 3 to 4 angstroms. The gA is univalent-catonic selective, and the proton is found to have a much faster transfer rate (>2X109 H+/S) in the gA channel that other univalent cations.
With its simplicity, the gA and the derivative channels intrigue interests in both experimental and computational fields. Recently, it has been found that the environment in which the gA channels reside affects the proton transport greatly. It is reported that the thickness of monoglyceride (GMO) bilayer modulated proton transfer through gA channels. As the membrane thickness decreases, the proton transport is enhanced. It is also found that proton transport rate in the gA channel in phosholipids is 10 times faster than that in GMO membranes. Also, a difference among PT in native and covalently linked gA channels is minimized when channels are embedded in phospholipids, but not in GMO membranes.
The aim of our research is to study the proton transport (PT) through gramicidin A and its correlation with the environmental membranes (GMO and DiPhPC, respectively) by means of classic molecular dynamic (MD) simulation and MS-EVB2 model. It is found that how gA channels are embedded inside the membrane is essential in the conformational change of protein, thus affecting the PT. The length of fA channel is about 25.5 angstroms, which is shorter than the thickness of both GMO and DiPhPC membranes. In DiPhPC membrane, the gA channel tends to be more flexible than in GMO membrane. Water molecules are more organized near DiPhPC's head group comparing to the water molecules near head groups of the GMO Lipids. By calculating the free energy profiles of proton through the channel as well as analyzing the conformation of both the channel and the lipids, a hypothesis for the influence of environmental membrane on PT through the channel is proposed (paper in preparation).
Our future research will be concerned with the aspects of PT through covalently linked gA channels (SS- and RR- dioxolane linked gramicidin A channels) as well as the transportation of sodium ions through gramicidin A channels.
