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