Another avenue of research has been to try and directly understand the impact of crystal size on framework flexibility and structural transition, by performing simulations of nanocrystallites without periodic boundary conditions. This line of research has been driven, in particular, by the Schmid group in Bochum. In 2019, Keupp et al. compared the thermal-and pressureinduced transformations of DMOF-1, between periodic systems and non-periodic nanocrystals. Like the above studies, they relied on a first-principles parameterized force field in order to make calculations faster -in this case, using the MOF-FF method. Combining direct MD and free energy methods, they could show that the free energy barrier for the transition is lower for small crystallites, through a nucleation-and-growth mechanism, than it is for a periodic system where the transition necessarily takes place in a concerted process. In later work, Schaper et al. refined this simulation protocol by providing a more explicit description of the mechanical pressure exerted on the system, introducing a mediating particle bath (similar to the pressure-transmitting medium used in experiments). In an alternate approach, the same authors also proposed an approach allowing the control of the volume of crystals by a tetrahedral tessellation of their instantaneous volume -enabling the use of free energy methods in nonperiodic systems. Both approaches make possible a detailed characterization of the transition mechanism, metastable states and intermediate structures of flexible MOFs like DUT-128 as a function of crystal size and thermodynamic parameters, as illustrated on Figure .