In solution, system 2 exists as a mixture of E,E and E,Z isomers, which undergo fast isomerization. We built an AA model for the E,E isomer of rotaxane 2 (Fig. ), while isomerization may occasionally occur within the timescale accessible by simulations. This was then immersed in a simulation box filled with explicit DCM solvent molecules, the same solvent used in the experiments, and with weakly coordinating PF - 6 anions (see Methods and SI for additional details). After preliminary energy minimization and short equilibration MD conducted in NPT periodic boundary conditions, we studied the system through classical MD simulation. Enhanced sampling (MetaD) was unnecessary in this system, as the timescale of shuttling dynamics is very fast and accessible within a practically attainable MD timescale.