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

TL;DR

A-CODE is a fully atomic, unified protein co-design model using multimodal diffusion that outperforms existing methods in protein and binder design, and can adapt to non-canonical amino acids.

Contribution

It introduces a fully atomic, one-stage protein co-design framework that surpasses prior two-stage models and enables modeling of non-canonical amino acids.

Findings

Outperforms all existing one-stage and two-stage design models.

Achieves a tenfold success rate improvement on hard binder design tasks.

Enables seamless adaptation to non-canonical amino acids.

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.