Advances in the determination of disordered protein ensemble

Intrinsically disordered proteins (IDPs) play essential roles in regulation, signaling, and phase separation, yet their structural complexity cannot be captured by a single conformation. Instead, they populate dynamic ensembles that encode a context-dependent function. Recent advances in experimental techniques coupled with physics-based simulations, coarse-grained models, and machine learning, have transformed our ability to generate and interpret IDP ensembles. Integrative frameworks now combine complementary data with computational approaches to refine ensembles at both local and global levels. Nevertheless, challenges remain in benchmarking, error estimation, and modeling assemblies involving protein–protein and protein–nucleic acid interactions. We highlight recent progress and outline the emerging directions that will shape the next generation of ensemble determination methods.