Mean free passage times (MFPTs) and free energy differences between the WPD-loop closed and open state for each system determined from our Markov state models (MSMs)a.
| Enzyme | Mean free passage time (μs) | ΔG (closed–open) (kcal mol−1) | |
|---|---|---|---|
| Closed → open | Open → closed | ||
| WT PTP1B | 1.6 ± 0.1 | 0.7 ± 0.02 | −0.5 ± 0.1 |
| Chimera 7 | 9.7 ± 0.9 | 1.1 ± 0.3 | −1.3 ± 0.2 |
| Chimera 4 | 171.6 ± 31.7 | 0.9 ± 0.1 | −3.1 ± 0.2 |
| Chimera 3 | 48.6 ± 8.3 | 0.3 ± 0.01 | −3.0 ± 0.1 |
| Chimera 1b | N.D. | N.D. | N.D. |
a
Errors for the MFPTs are the standard deviations obtained from the Bayesian calculation. Free energy differences were obtained by calculating the equilibrium constants from the MFPTs with errors calculated by propagating the errors in the MFPTs to the free energy calculations and taking the largest possible difference (see the Materials and methods).
b
The MFPTs for Chimera 1 could not be reliably determined as the WPD-loop open state has too small a population for a cluster center to be placed there.