About this episode

John Jumper discusses the impact of AlphaFold on protein folding and its limitations.

This episode is sponsored by Notion. Learn more about Notion's Developer Platform today at https://notion.com/mlstProtein folding stalled biology for fifty years. A sequence of amino acids dictates a three-dimensional shape, but reading that shape meant a year and roughly $100,000 of crystallography per structure. Then AlphaFold 2 won CASP14 so decisively the organizers called the problem essentially solved.In this documentary cut, John Jumper, who shared the 2024 Nobel Prize in Chemistry and has since left DeepMind for Anthropic, walks Tim Scarfe through what the system did and, more interestingly, what it did not. The architecture gets a proper dissection: MSAs, the Evoformer, invariant point attention, the FAPE loss, and Jumper's correction of the equivariance story, which ablations valued at roughly 2.5 of 30 GDT points rather than the whole win. He is blunt about the limits. AlphaFold predicts one experiment extraordinarily well; it is not a model of the cell, it does not capture dynamics, and on a given drug target it is "wrong nine times out of ten."From there: the AlphaFold Database of 200M+ predicted structures, AlphaFold 3 and ligands, Isomorphic Labs, and…

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