In a previous study¹, we reported the discovery of a protein that oligomerizes in a fractal-like pattern. This assembly is relies on conformational flexibility, leading to slightly varied interfaces as the complex grows. Our initial investigation focused on the formation requirements of this fractal structure using static modeling techniques. In this follow-up project, our goal is to understand the structural and energetic differences between interfaces in assemblies of varying sizes. We have obtained cryo-EM structures of assemblies multiple sizes, which have undergone refinement and preliminary molecular simulations. These initial results indicate that the models are of good quality. To deepen our understanding, we plan to carry out enhanced-sampling molecular dynamics simulations. These will allow us to compute the free energy differences between the various interface types. The insights gained will inform on the energetic landscape of the fractal assembly process. Due to the large size of these assemblies and the complexity of identifying an appropriate collective variable to describe the structural transitions, the proposed simulations are expected to be computationally demanding and will require sufficient storage for the resulting data. 1 F. Sendker et al. (2024). Emergence of fractal geometries in the evolution of a metabolic enzyme. Nature 628: 894–900.