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arXiv · 2605.03360

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
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Abstract

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 designability for unconditional protein generation, outperforming all existing one-stage and two-stage design models. For binder design, A-CODE rivals and even outperforms existing state-of-the-art two-stage design models and, compared with the existing one-stage co-design model, achieves a drastic tenfold improvement in success rate on hard tasks. The inherent flexibility of our atomic formulation enables, for the first time, seamless adaptation to non-canonical amino acid (ncAA) modeling. Our fully atomic framework establishes a new, versatile foundation for all-atom generative modeling that can be naturally extended to complex biomolecular systems.

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Chaoran Cheng, Jiaqi Guan, Milong Ren, Chengyue Gong, Cong Liu, Xinshi Chen, Ge Liu, Wenzhi Xiao. 2026-05-05. A-CODE: Fully Atomic Protein Co-Design with Unified Multimodal Diffusion. https://arxiv.org/abs/2605.03360

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