Fig. 4.

Mean first-passage times between states within the four conformational regions (active: blue, inactive: red, intermediate I: magenta, and intermediate II: green) marked by black dotted lines as shown in Fig. 1 for (A) the methadone-bound MOR, (B) the morphine-bound MOR, and (C) the TRV130-bound MOR systems. The timescales are reported in milliseconds. Arrow thickness connecting the different states is proportional to the corresponding transition probabilities. The circle area is proportional to the total equilibrium probability of the different states. The macrostates that form part of each of the states depicted in the four regions are listed in Supplemental Table 8.