An all-atom foundation model for intrinsically disordered proteins.
Instead of predicting one static structure, Topos-1 generates atomic-resolution conformational ensembles: the full distribution of shapes a protein occupies. It outperforms AlphaFold-2, Boltz-2, Chai-1, and BioEmu on key experimental benchmarks, cutting ensemble Rg error by 43–79%, while running about 1,000× faster than molecular dynamics. Its ensembles were successfully used to rank internal small-molecule candidates against a disordered prostate-cancer target in agreement with lab-measured potencies.