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Podcast Episode

The art of protein design with AI

Hard Drugs··15 October 2025·1h

About this episode

What if you could design a protein never seen in nature? In this episode, Jacob and Saloni explore how researchers are using new tools like RFDiffusion, AlphaFold, and ProteinMPNN to ‘hallucinate’ entirely novel proteins: designing them from scratch to solve problems evolution hasn’t tackled. They talk about how these technologies could transform medicine, agriculture, and materials science. Along the way, they reflect on the surprising ways AI is changing the process of science itself. Hard Drugs is a new podcast from Works in Progress and Open Philanthropy about medical innovation presented by Saloni Dattani and Jacob Trefethen. Saloni’s substack newsletter: https://www.scientificdiscovery.dev/ Jacob’s blog: https://blog.jacobtrefethen.com/  Courses: EMBL-EBI. AlphaFold: A practical guide https://www.ebi.ac.uk/training/online/courses/alphafold/  Articles: Tanja Kortemme (2024) De novo protein design—From new structures to programmable functions https://www.cell.com/cell/fulltext/S0092-8674(23)01402-2  Jie Zhu et al. (2021) Protein Assembly by Design https://pubs.acs.org/doi/10.1021/acs.chemrev.1c00308  Lectures: Rosetta Commons (2024) Diffusion models for protein structure generation (and design) https://www.youtube.com/watch?v=OEnY2yA3jy8  Rosetta Commons (2024) AlphaFold – ML for protein structure prediction https://www.youtube.com/watch?v=SVrn8_8aKO8  Rosetta Commons (2024) MPNN – ML for protein sequence design https://www.youtube.com/watch?v=6z4XmUAwdNA  Acknowledgements: Aria Babu, editor at Works in Progress Graham Bessellieu, video editor Rachel Shu, on-site editor Anna Magpie, fact-checking Abhishaike Mahajan, cover art Atalanta Arden-Miller, art direction David Hackett, composer Works in Progress & Open Philanthropy