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

SPECIFIC COMPUTATIONAL METHODS: In the QM calculations reported here, we have obtained the structures of the energy minima by optimization at HF/6-31G* level. This includes exchange but not correlation energy, in addition to all those terms that have classical analogues (kinetic energy, electronnuclear interaction, and electron-electron and nuclear-nuclear repulsion). However, the omitted correlation energy, while the smallest term, is still not negligible in determining the differences in energy c) Providing a hypothesis that shows much of the remainder of a path that a proton could follow from gate to the extracellular surface of the membrane. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 d) Considering several experiments that are typically ignored or interpreted in contradictory fashion in order to fit them to the standard model, when more natural interpretations are consistent with proton transport. e) Consideration of analogous systems, such as H v 1, cytochrome c, bacteriorhodopsin, and the flu M channel that are known to transmit protons, It is of particular interest that all of these, like the VSD of the K v channel, have the same tyrosine-arginine-glutamate arrangement in the apparent proton path, as well as other similarities (e.g., an RER/RDR triad) that would create a proton path. It would be of interest to investigate other proteins that transmit protons to determine whether this triad is a recurring motif in proton transport in proteins.