Figure 9. Overlap of eBDIMS forward and reverse pathways with free energy landscapes obtained from atomistic simulations.

(a) RBP opening with biased MD trajectories (1 μs); (b) SERCA headpiece spontaneous closing in multi-run MD simulations from the open conformation 1su4 (2 μs) reaching the intermediate state cluster; (c) GLIC spontaneous closing in a single long 1 μs-simulation at pH=7 and (d) opening in a 500 ns simulation at pH=4.6. Note that the slightly divergent pathways enclose most of the lowest energy passage between the end-states, with the approached crystallographic intermediates distributed at the boundaries.