Quantitative comparison of cryo-EM density maps and conformations from the MD simulation. (A) Time series of the cross-correlation (CC) between protein conformations in the apo simulations md0–md2 and the experimental density maps SP3sym (corresponding to the fully Zn-bound structure, blue line) and SP2 (apo structure, orange line), together with the distribution of the CC, drawn as KDEs. (B) Comparison of best-fit conformation from the apo MD simulations (ignoring the initial 100 ns during which the system relaxes) to the SP2 density at a contour level of 0.32 (6 σ): snapshot from apo md1 at 369 ns with CC = 0.28, shown as a magenta dot in A. Two views are shown at 90° orientations. (C) Comparison of the same apo MD snapshot to the SP3sym density at a contour level of 0.6 (6 σ). (D) CC time series of the holo simulations md0-md2 to SP3sym (blue) and SP2 (orange) density maps. (E) Comparison of best-fit conformation from the holo MD simulations (ignoring the initial 100 ns during which the system relaxes) to the SP2 density: snapshot from holo md0 at 301 ns with CC = 0.34, shown as a cyan dot in D. (F) Comparison of the same holo MD snapshot to the SP3sym density.