Metal-organic frameworks (MOFs) are a class of nanoporous materials characterized by exceptional chemical and physical properties, which are very attractive for applications in the fields of gas storage and separation, catalysis, drug delivery and more. Recently, it has been discovered that certain MOFs, the so-called flexible MOFs, possess a highly ordered network but yet show the ability to structurally transform between different crystalline phases. To date, the molecular origin of this behavior is not well understood. However, to explore the immense potential of these flexible MOFs to functional applications, such understanding is prerequisite. Essential in this respect is knowledge of the free energy surface (FES) of the material as a function of the relevant molecular degrees of freedom, which governs the observed flexible behavior. However, as yet it remains elusive how complicated transformations, such as those related to concerted transitions of multiple flexible building blocks, can be modeled computationally. Within this proposal a general framework will be developed based on enhanced sampling molecular dynamics simulations, which allows one to explore the interesting regions of phase space to generate, interpret, and analyze the FES of various MOFs covering a wide range of flexible modes. The research will be performed in close collaboration with various experimental partners who have access to experimental thermodynamic and kinetic properties of these MOFs.