The Energetics of Arginine-Lipid Interactions with Implications for Ion Channel Gating
Apr 24, Wed 2007
3:00pm, MRB Conference Room
Department of Chemistry, University of California, Davis
Biological membranes consist of bilayer arrangements of lipids forming a hydrophobic core that presents a physical barrier to all polar and charged molecules. This long-held notion has recently been challenged by biological translocon-based experiments that report small apparent free energies to insert charged side chains near the center of atransmembrane helix.
We have carried out extensive fully atomistic molecular dynamics simulations to provide a free energy profile for moving a transmembrane helix containing an Arg side chain across a lipid bilayer. These simulations reveal a significant free energy barrier and provide us with atomic-scale views of the controlling mechanisms.
Our findings have implications for the gating mechanisms of voltage gated potassium channels, suggesting that movements of protonated ARG residues through the center of the membrane will be prohibited.