Stability of the dimer interface in MD simulations. (A) Dimeric interactions in the TMD quantified as the fraction of native contacts (from PDB accession no. 5VRF) retained over the course of the simulations for apo (purple) and holo (cyan) states. Time series for all three repeats were averaged over 20-ns intervals (solid line) with 95% confidence intervals shown as transparent bands. Distributions (KDEs) from all data are shown on the right. (B) Snapshots from a holo MD simulation (md1) at the indicated times showing the TMD native contact residues (K79, L83, L86, A87, A90, F91, M93, G94, S95, F97, L98, L99, Y102, E105, L207, and L208) and CTD native contact residues (R237, G255, L257, S258, L259, N260, H263, E281, I283, I284, H285, Q286, D287, and P288) in cyan. Magenta spheres represent Zn ions. The membrane, water, and other ions are omitted for clarity. (C) Dimeric interactions in the CTD as in A. (D) Snapshots from an apo simulation (md1) at the indicated times showing that dimeric interactions remain intact despite large interdomain movements. (E) Change in the angle between TMD and CTD from MD simulations. The angle corresponds to that required for optimal superimposition of the Cα atoms from the CTD to the reference structure (5VRF) at each time point in the MD trajectory. This angle was determined after aligning the TMD with the starting structure.