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We run a number ofexploratory OPES simulations where, in about100 ns, we observe a few forth and back subunit exchange events (see SI) that occur smoothly without passing via unnaturalconformations, reflecting the use of meaningful CVs (see movie inthe SI). Calculating an accurate free energysurface is beyond present-day capabilities, given the size and complexityof the system. However, we found it of interest to determine, evenif in an approximate form, the free energy barrier corresponding tothe subunit flip (see SI).

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