Hacking proteins with AI

Nature didn’t evolve all the proteins we need, but maybe artificial intelligence can help. Jacob and Saloni explore how tools like AlphaFold and ProteinMPNN are helping researchers re-engineer proteins, to make them safer, more stable, and more effective. They talk about how new technologies could help make a long-sought vaccine against Strep A, which causes scarlet fever and rheumatic heart disease, and how similar tools have already led to breakthroughs against COVID and RSV.
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: scientificdiscovery.dev

Jacob’s blog: blog.jacobtrefethen.com
Courses:
• EMBL-EBI. AlphaFold: A practical guide ebi.ac.uk/training/online/courses/alphafold

Articles:
• Monica Jain et al. (2022) Exosite binding modulates the specificity of the immunomodulatory enzyme ScpA, a C5a inactivating bacterial protease. pmc.ncbi.nlm.nih.gov/articles/PMC9464890
• Jakki Cooney et al. (2008) Crystal structure of C5a peptidase rcsb.org/structure/3EIF
• Hui Li et al. (2017) Mutagenesis and immunological evaluation of group A streptococcal C5a peptidase as an antigen for vaccine development and as a carrier protein for glycoconjugate vaccine design pubs.rsc.org/en/content/articlelanding/2017/ra…

Lectures:
• Rosetta Commons (2024) AlphaFold – ML for protein structure prediction youtube.com/watch?v=SVrn8_8aKO8
• Rosetta Commons (2024) MPNN – ML for protein sequence design youtube.com/watch?v=6z4XmUAwdNA

Acknowledgements:
• Aria Babu, editor at Works in Progress
• Graham Bessellieu, video editor
• Rachel Su, on-site editor
• Anna Magpie, fact-checking
• Abhishaike Mahajan, cover art
• Atalanta Arden-Miller, art direction
• David Hackett, composer

Works in Progress & Open Philanthropy