The Role of Proton Transport in Gating Current in a Voltage Gated Ion Channel, as Shown by Quantum Calculations

Alisher M Kariev; Michael E Green

Fleming, Moon, and coworkers have considered the thermodynamics of inserting various side chains into a membrane (101) . Their focus has been on bacterial outer membrane proteins (OmpA, and other outer membrane proteins, which are essentially beta barrels that allow substances through the outer membrane of gram negative bacteria). The relevance to the K v VSD is that they find that it is fairly difficult to insert arginine, considered as a charged residue. If gating required charged residues to move through the headgroup region into the extracellular space to open the channel, or else intracellularly to close it, it would be difficult. While these authors considered only the insertion of the protein (unidirectional) to . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/371914 doi: bioRxiv preprint the membrane, the channel, if it leaves and reenters would not be stabilized by a drop in free energy, since it must go up the free energy gradient in one direction. This suggests that the extent of travel of S4, on the standard assumption that the arginines are charged, must be limited to keeping the charges within the membrane, and almost certainly within the hydrophobic part of the membrane. If the arginines are not charged this does not apply, but then the arginines would not contribute to gating current.