Supplementary Figure 4: Initial placement and ATP coverage of the channel for the MSM construction.

(a) Blue spheres represent the β-phosphate atom of all 453 ATP configurations used to initiate MD simulations. The mVDAC1 channel is represented with the β-barrel in cyan and the N-terminal helix in red. The majority of simulations start with ATP in the pore domain. Membrane boundaries are indicated by black bars, but lipid and water are not shown for clarity. (b) Blue dots represent the β-phosphate of ATP plotted every 20 ps from all MD simulations initiated in panel a. The aggregate simulation time was 40 μs, and there are 10,000,000 ATP configurations represented. The densest regions are in the channel around the helix indicating that configurations in the pore domain were highly sampled. (c) Extent of ATP motion during each individual simulation. The starting z position (blue dot) and range of motion (green bar) of the COM of the ATP for each of the 453 MD simulations. The ATP undergoes 10–20 Å movements in many simulations, but never crosses the entire channel.