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First Ever  /  Biology

A single-stage AI can now design the entire atomic structure of a protein at once, including synthetic parts that do not exist in nature.

Traditional protein design is a slow, two-part process that first picks a shape and then tries to find a matching sequence. This new diffusion model handles both the sequence and the physical coordinates of every atom simultaneously. This unified approach allows researchers to incorporate non-canonical amino acids that are entirely synthetic. Designing proteins with these alien building blocks could lead to ultra-stable enzymes for industry or completely new types of medicines. It moves us past the limited palette of 20 natural amino acids that has governed life for billions of years.

Original Paper

A-CODE: Fully Atomic Protein Co-Design with Unified Multimodal Diffusion

Chaoran Cheng, Jiaqi Guan, Milong Ren, Chengyue Gong, Cong Liu, Xinshi Chen, Ge Liu, Wenzhi Xiao

arXiv  ·  2605.03360

We present A-CODE, a fully atomic unified one-stage protein co-design model that simultaneously refines discrete atom types and continuous atom coordinates. Unlike predominant two-stage methods that cascade structure design with amino acid-level sequence design, our approach is fully atomic within a unified multimodal diffusion framework, in which residue identities are inferred solely from atom-level predictions. Built upon the powerful all-atom architecture, A-CODE achieves superior designabil