Code to complex: AI-driven de novo binder design
Daniel R Fox1, Cyntia Taveneau2, Janik Clement3
1Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia; Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre for Electron Microscopy of Membrane Proteins, Monash Institute of Pharmacological Sciences, Parkville, VIC 3052, Australia; AI Protein Design Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, Australia.
Abstract:
The application of artificial intelligence to structural biology has transformed protein design from a conceptual challenge into a practical approach for creating new-to-nature proteins. By leveraging machine learning, researchers can now computationally design proteins with tailored architectures and binding specificities. This has enabled the rapid in silico generation of high-affinity binders to diverse and previously intractable targets. This approach dramatically reduces binder development time and resource requirements, compared to traditional experimental approaches, while improving hit rates and designability. Recent successes include the creation of binding proteins that neutralize toxins, modulate immune pathways, and engage disordered targets with high affinity and specificity. Improvements in model accuracy are expanding the scope of what can be designed, while characterization in preclinical models is paving the way for therapeutic development. De novo binder design represents a paradigm shift in protein engineering, where custom binders can now be programmed to meet specific biological challenges.
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