Integrative structural biology

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The structural determination of large molecular complexes is a formidable challenge, as they can exist in multiple functional conformations and compositions, they can interact with biological membranes, they can be regulated by post-translational modifications (PTMs) and are affected by the crowded conditions of the native environment. All these aspects currently limit the possibility of gaining high resolution information about their functional conformational landscape. While techniques like cryo-EM have been transformative to approach this problem, there are cases where a computationally-driven integrative approach remains the strategy of choice. Within this framework we have been tackling highly flexible multi-domain systems and complexes in direct contact with membrane bilayers, which are elusive to canonical structural determination and biophysical characterisation.