Although plain MD yielded a few trajectories that completed THI, many more such runs would be needed to obtain better precision for THI rate constants . Therefore, we instead used an enhanced sampling technique, the weighted ensemble method implemented in WESTPA , to compute the THI rate constant. In WESTPA, a collection of MD replicates initiated from metastable form is managed by cloning new ones in regions of the conformational space with fewer replicates, and merging existing ones in regions with more replicates, to generate a more even distribution of replicates along desired progress coordinates. This allows an artificial increase in the number of replicates that sample higher energy transitional regions. Correct statistics is maintained by adjusting replicate weights when replicates are cloned or merged. Note that this method does not involve modifying the Hamiltonian. As detailed in Results and Discussion, THI progress coordinates were defined for each motor in terms of key structural features, such as dihedrals describing rotation around the central double bond and rotor/stator puckering coordinates. Then the conformational space was divided into bins of different progress coordinate values, and WESTPA was used to monitor the number of MD replicates in each bin to decide when to clone or merge replicates. When a replicate reached the bin defining the stable form of the motor, the replicate was restarted at one of the initial metastable conformations. As the probability distribution across bins converge to steady state distribution, the THI rate constant is calculated using the steady state flux from the metastable form to the stable form.