TABLE 2.

Transition rates of the post-optimization wild type model.

States	Transition rates
IC3 →IC2, C3→C2, BC3→BC2	α11 = Tf × 8.5539/(6.59e-2×exp(−v/(17.0))+2.76e-1×exp(−v/(150)))
IC2→IF, C2→C1, BC2→BC1	α12 = Tf × 8.5539/(6.59e-2×exp(−v/(15.0))+2.76e-1×exp(−v/(150)))
C1→O, BC1→BO	α13 = Tf × 8.5539/(6.59e-2×exp(−v/(12.0))+2.76e-1×exp(−v/(150)))
IC2→IC3, C2→C3, BC2→BC3	β11 = Tf × 6.98e-2×exp(−v/20.3)
IF→IC2, C1→C2, BC1→BC2	β12 = Tf × 3.04×exp(−(v-5)/20.3)
O→C1, BO→BC1	β13 = Tf × 1.18×exp(−(v-10)/20.3)
IC3→C3, IC2→C2, IF→C1	α3 = Tf × 8.06e-6×exp(−v/(8.43))
C3→IC3, C2→IC2, C1→IF	β3 = Tf × 6.45×exp((v)/(1.48e1))
O→IF	α2 = Tf × 3.54×exp(v/(3.81e1))
IF→O	β2 = (α13×α2×α3)/(β13×β3)
O→IS	βx = 2.30e-2×α3
IS→O	αx = 3.02e-2×α2
C3→BC3, C2→BC2, C1→BC1, O→BO	µ1 = 1.70e-07
BC3→C3, BC2→C2, BC1→C1, BO→O	µ2 = 5.66e-04

The first column indicates state transitions, while the second column specifies their corresponding transition rate names and equations. “Tf” is a temperature scaling factor calculated from a Q10 of 3 as described in the Supplementary Material of this work. Nomenclature for transition rates and affinities: charged drug (+), neutral drug (n), closed states (c), inactivated states (i), bursting states (b), drug binding to the channel (on), drug unbinding from the channel (off).