The coupled proton transport in the ClC-ec1 Cl(-)/H(+) antiporter

Using a reactive molecular dynamics simulation methodology, the free energy barrier for water-mediated proton transport between the two proton gating residues Glu(203) and Glu(148) in the ClC-ec1 antiporter, including the Grotthuss mechanism of proton hopping, was calculated. Three different chloride-binding states, with 1), both the central and internal Cl(-), 2), the central Cl(-) only, and 3), the internal Cl(-) only, were considered and the coupling to the H(+) transport studied. The results show that both the central and internal Cl(-) are essential for the proton transport from Glu(203) to Glu(148) to have a favorite free energy driving force. The rotation of the Glu(148) side chain was also found to be independent of the internal chloride binding state. These results emphasize the importance of the 2:1 stoichiometry of this well-studied Cl(-)/H(+) antiporter.