Snapshots along the simulation.

<p><b>A:</b> Front (top row) and side (bottom row) views of snapshots taken at 0, 2.5, 5, 7.5, and 10 ns of the targeted molecular dynamics trajectory, showing the protein in ribbon representation. The predicted pore is shown in each snapshot in blue (radius > 3 Å), green (3 Å > radius > 1.8 Å), and red (radius < 1.8 Å), with red indicating a constriction too narrow to allow passage of a chloride ion. Over the first 5 ns, we observe the NBDs coming together, and increased bending in the intracellular loops (ICLs), although the transmembrane pore remains occluded. At 7.5 ns, we note that the ICLs have straightened out as the NBDs become even more tightly bound, and the conformational wave moves up to the transmembrane region where a through pore open to chloride conduction is first seen. At the end of the simulation (10 ns), tight coupling of the NBDs is complete, and the open pore is observed. <b>B:</b> Schematic representations of the fully dissociated C0, partial dimer C1, full-dimer closed transition state C2, and O open state configurations that likely correspond to the structures observed in the TMD simulation.