It is now agreed upon that there is more than one Q binding site in the Q tunnel (Fig. ). The Q binding sites (sites 1-5, Fig. ), which were predicted based on computer simulations , have all been consolidated by structural data , even though biochemical evidence is lacking. The sites 1 and 2 are near the N2 FeS center, whereas the sites 4 and 5 are closer to the entrance of the Q tunnel. A possible Q binding site outside the Q tunnel has also been proposed based on computer simulations and site-directed mutagenesis . At site 1, Q binds within the electron transfer distance to N2 FeS cluster (10-12 Å), whereas at site 2, Q binds outside of the biologically-relevant electron transfer range (ca. 16 Å). It has been suggested that after two-electron reduction of Q at site 1, it moves to site 2, which helps in preventing unfavorable back electron transfer and enhancing rate of forward turnover (see also ). Alternatively, site 2 may also correspond to a Q binding pose prior to its binding to site 1 for its reduction . The role of the sites closer to the entrance (sites 4 and 5) is not entirely clear. However, several recent proton pumping models of complex I considered the sites closer to the entrance as an important component of the coupling mechanism , although details differ in each of these models (see section 2).