Table 1. Kinetic and thermodynamic parameters for the B–E exchange process obtained from an analysis of temperature dependent CPMG RD NMR experiments, a 19 state MSM and direct MD simulations ^a .

Temp (°C)	k ex (s–1)	p E (%)	Source
1.0	649 ± 50	4.7 ± 0.2	CPMG RD NMR
5.3	1099 ± 57	4.7 ± 0.2	CPMG RD NMR
10.4	2240 ± 122	3.8 ± 0.5	CPMG RD NMR
15.4	3871 ± 79	3.5 ± 0.2	CPMG RD NMR
20.4	6100 ± 350	3.6 ± 0.6	CPMG RD NMR
37	3.9 ± 0.3 × 104	2.3 ± 0.3	Arrhenius extrapolation of CPMG RD NMR derived rates
37	3.3 ± 0.4 × 105	1.4 ± 1	19 state MSM (2 state analysis)
50	1.3 ± 0.3 × 105	1.9 ± 0.3	Arrhenius extrapolation of CPMG RD NMR derived rates
50	6.6 ± 0.3 × 105	0.6 ± 0.3	19 state MSM (2 state analysis)

Transition path time (ns)
	Average value	Range	Source
37	60.5	2.4 to 231.2	MD simulations
50	39.6	1.3 to 141.6	MD simulations

^aTo estimate two state exchange parameters from the 19 state MSM 1/k_ex was taken to be the slowest implied timescale as it corresponds to the E–B interconversion (Fig. 3) and states E and B were defined in terms of the populations of states 0 (E) and 15–18 (B), respectively. The fractional population of state E, p_E, was then calculated as the population of state 0/(sum of populations of states 0 and 15–18). The value of p_B = 1 – p_E.