Atomic functional site scaffolding in biopolymers with RFdiffusion3.

RFdiffusion3 (RFD3) rapidly and accurately designs biopolymers with complex atomic constraints, producing active catalysts in zero-shot 96 construct campaigns.

• Why it matters: Understanding and replicating the precise atomic arrangements in biomolecules is crucial for advancing enzyme and RNA design, yet existing methods struggle with complex constraints.
• What they did: The authors developed RFD3, a generative AI employing free atom diffusion, and demonstrated its effectiveness through experimental design of enzymes and RNA structures, including phosphotriesterases and zinc proteases.
• The result: Active catalysts were obtained in both cases without prior optimization, indicating RFD3's potential to accelerate the creation of functional biomolecules with intricate atomic architectures.