Video 1

Movie S1. Hybrid QM/MM MD simulation of proton transfer from the N-side of the membrane along a water chain to conserved glutamates. Starting from a hydronium ion (H3O+) placed initially at the N-side opening, the proton diffuses within ∼1 ps over a distance of ∼11 Å to Glu-72K, alternating between hydronium (H3O+) and Zundel (H5O2+) structures in a Grotthuss-type fashion. The hydroxyl group of residue Thr-160N helps stabilize the water chain through hydrogen bonding, but does not participate directly in the proton transfer process. The dynamics of the hydrogen-bonded network is shown in Fig. S2.