Additional complementary insight into molecular behavior is provided by a Markov state model (MSM) analysis of the MD trajectories. Figure shows the result of applying the pyEMMA analysis suite to the solvent molecule MD trajectories. In the case of the acetone solvate, two components are identified that account in total for > 95% of the variance of the motion. A free energy plot obtained by projecting the trajectories into this space, Figure (a), shows four distinct minimum energy states. As illustrated in Figure of the Supplementary Information, the MD trajectory can be clustered according to these states, allowing representative snapshots, Figure (c), to be extracted, which correspond to four distinct "orientations" of the acetone within the cavity. These macrostates are related by a C2 axis (respecting the molecular symmetry) and an inversion centre (respecting the symmetry of the cavity).