Module 8: The Creator

De Novo Design

Generate proteins that have never existed using RFdiffusion and the full design pipeline.

• Explain what de novo design means, and what separates it from redesigning an existing protein
• Describe how a diffusion model builds a backbone by iteratively denoising random residue positions and orientations
• Choose hotspot residues for binder design from conservation, exposure and spatial clustering
• Walk the modular pipeline end to end: target and hotspots → RFdiffusion → ProteinMPNN → AlphaFold2
• Judge generated binders against the published in-silico filters, including the judgement to reject all of them