Based on chemical biology data , a second site in the Q tunnel near the E channel-Q tunnel junction was proposed, which corresponds to the region near site 4 (see Fig. ) . Computer simulations of a Q modelled at this site (23) revealed a hydrated connectivity that linked the Q site 4 (and also 5) to the membrane-bound subunits via the E channel (Fig. ). This raised the possibility of a proton transfer between the Q tunnel region and the membrane bound subunits through the conserved acidic residues and water molecules found in the E channel (see also ). The latter region has indeed been scrutinized with computational approaches to study the possibility of proton transfer through it . Now, several recent proton pumping models have considered the E channel region to be protonconducting and a key coupling element for the redox activity in the Q tunnel and proton pumping in the membrane domain. However, direct experimental evidence of this is missing.