Professor Toby Allen
Department of Chemistry
University of California, Davis
Davis, California

Monday, September 10, 2007
3:00 pm (CT)
3269 Beckman Institute

Abstract

Biological membranes exhibit bilayer arrangements of lipid molecules that present a physical barrier to charged molecules. This long-held view has recently been challenged by translocon-based experiments that report small free energies to insert charged side chains in the middle of a transmembrane helix. We provide a renewed theoretical picture of charge movement in membranes by calculating free energy profiles of an arginine side-chain, isolated or attached to a transmembrane α-helix, through a lipid bilayer, using fully atomistic simulations. Despite penetration of water and lipid head groups to interact with the side chain, the free energy barrier is large. We explain the difference in our microscopic free energy barrier and translocon results by carrying out studies on the leader peptidase protein. Furthermore, we have computed a pKa profile to discover that, while some portion of arginine will take the deprotonated form in the membrane, the large free energy barrier is maintained. Our findings have implications for the gating mechanisms of voltage gated ion channels, suggesting that large movements of lipid-exposed arginine side chains are unlikely.