100 snapshots were extracted from each sMD trajectory (200 total per model), equally sampling the WPD loop RMSD range, using cpptraj v4.25.6 (AmberTools20). The systems were resolvated and reequilibrated as outlined above and 50 ns equilibrium MD simulations were carried out with Amber20 via BioSimSpace, saving snapshots every 10 ps (5000 frames per simulation). Total sampling time of trajectories used for a single MSM was 10 µs.