(1) the starting crystal structure (substrate in an "IN" conformation), and (2) snapshots of substrate "IN" and "OUT" conformations from our MD simulations. While the simulations initiated from the crystal structures give good agreement with experiment (see Figure and Table ), the snapshots from our MD simulations give higher barriers than experiment and calculations initiated from the crystal structure. This is in agreement with previous work comparing the impact of pulling snapshots from MD simulations from DFT-based QM/MM simulations vs. using the crystal structure (see e.g. ref. ), and is likely due to structural distortion during the MD simulations.