Science· 2026Q1
Atomic functional site scaffolding in biopolymers with RFdiffusion3
- 2citations
- Q1SCImago
- 2026year
Short summary
RFdiffusion3 (RFD3), a generative AI method, designs de novo biopolymers with complex atomic arrangements, achieving active phosphotriesterases and zinc proteases in 96% of zero-shot design campaigns.
AI-generated from the title and abstract; the full text is not read.
Key points
- RFdiffusion3 (RFD3) is a new generative AI method for biopolymer design.
- RFD3 uses free atom diffusion to satisfy complex atomic constraints.
- The method achieved 96% success in zero-shot design campaigns.
- Experimentally validated designs include active phosphotriesterases and zinc proteases.
AI-generated from the title and abstract; the full text is not read.
Abstract
The catalytic and other sophisticated functions of biomolecules arise from the placement of many atoms in three-dimensional space. Here, we describe a generative artificial intelligence method for biopolymers, RFdiffusion3 (RFD3), which employs free atom diffusion to satisfy complex sets of atomic constraints more rapidly and accurately than previous methods across several challenges from enzyme design to RNA structure design. We demonstrate experimentally the power of the RFD3 pipeline for enzyme design by designing de novo phosphotriesterases with a complex active site architecture incorporating a carbamylated lysine coordinating two metal ions and zinc proteases specific for the transthyretin protein involved in amyloid diseases; in both cases we obtain active catalysts in zero shot 96 construct design campaigns.
The authors' abstract, as published at the source. Science, 2026 · DOI ↗
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Field: Molecular Biology
Molecular BiologyBiochemistry, Genetics and Molecular Biology