Toby Allen, Ph.D.
Department of Chemistry
UNIVERSITY OF CALIFORNIA, DAVIS

View this lecture live ->
Use user name guest and no password

Biological membranes exhibit bilayer arrangements of lipid molecules in which hydrocarbon is segregated away from the aqueous phase to form a hydrophobic core region that presents a physical barrier to all polar and charged molecules. This long-held view has recently been challenged by biological translocon-based experiments that report small apparent free energies to insert charged side chains in the center of a transmembrane helix. We present the free energy profile of a protonated Arg side-chain, attached to a transmembrane ±-helix, through a lipid bilayer, obtained using fully atomistic molecular dynamics simulation. Despite considerable membrane perturbations the free energy barrier is ~17 kcal/mol.

We explain the difference in our microscopic free energy barrier and experimental results using free energy calculations of the Leader peptidase which demonstrate that a protonated Arg will reside closer to the interface than the center of the membrane. Our findings have significant implications for the gating mechanisms of voltage gated potassium channels, suggesting that large paddle-like movements of lipid-exposed protonated Arg residues will be prohibited.