Hacking proteins with AI

Описание: 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.

00:00 Hacking proteins with AI
03:21 What makes proteins cool
05:29 Can we make a vaccine against Strep A?
10:12 Proteins in nature aren’t enough, and we can improve them with AI
21:12 ProteinMPNN and AlphaFold are transforming drug design
29:52 A short history of protein structure prediction from physical models to deep learning
34:48 Using AI to design a Strep A vaccine
39:27 Validating an AI-designed Strep A vaccine
43:09 Recent AI protein breakthroughs
49:30 Why we don’t already have a Strep A vaccine and the future of optimizing protein drugs

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...
Articles:
Monica Jain et al. (2022) Exosite binding modulates the specificity of the immunomodulatory enzyme ScpA, a C5a inactivating bacterial protease. https://pmc.ncbi.nlm.nih.gov/articles...
Jakki Cooney et al. (2008) Crystal structure of C5a peptidase https://www.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 https://pubs.rsc.org/en/content/artic...
Lectures:
Rosetta Commons (2024) AlphaFold – ML for protein structure prediction    • AlphaFold – ML for protein structure predi...  
Rosetta Commons (2024) MPNN – ML for protein sequence design    • MPNN - ML for protein sequence design  

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