A-CODE presents a fully atomic one-stage multimodal diffusion model for protein co-design that claims superior unconditional generation performance over prior one- and two-stage models plus a tenfold success-rate gain on hard binder-design tasks.
La-proteina: Atomistic protein generation via partially latent flow matching.arXiv preprint arXiv:2507.09466
7 Pith papers cite this work. Polarity classification is still indexing.
abstract
Recently, many generative models for de novo protein structure design have emerged. Yet, only few tackle the difficult task of directly generating fully atomistic structures jointly with the underlying amino acid sequence. This is challenging, for instance, because the model must reason over side chains that change in length during generation. We introduce La-Proteina for atomistic protein design based on a novel partially latent protein representation: coarse backbone structure is modeled explicitly, while sequence and atomistic details are captured via per-residue latent variables of fixed dimensionality, thereby effectively side-stepping challenges of explicit side-chain representations. Flow matching in this partially latent space then models the joint distribution over sequences and full-atom structures. La-Proteina achieves state-of-the-art performance on multiple generation benchmarks, including all-atom co-designability, diversity, and structural validity, as confirmed through detailed structural analyses and evaluations. Notably, La-Proteina also surpasses previous models in atomistic motif scaffolding performance, unlocking critical atomistic structure-conditioned protein design tasks. Moreover, La-Proteina is able to generate co-designable proteins of up to 800 residues, a regime where most baselines collapse and fail to produce valid samples, demonstrating La-Proteina's scalability and robustness.
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Steerable NODEs extend manifold neural ODEs by coupling base flow on homogeneous spaces with parallel transport of features in associated bundles, achieving G-equivariance under invariant conditions.
DISCO co-designs protein sequence and structure to produce functional heme enzymes that catalyze several new-to-nature carbene-transfer reactions at activities exceeding prior engineered enzymes.
CCDD defines a joint multimodal diffusion on continuous representation space and discrete token space to combine expressivity with explicit token supervision for diffusion language models.
A novel neural architecture based on Pairformer is introduced for learning committor functions to better capture dynamical features in biomolecular rare events without specialized priors.
Yeti is a compact tokenizer for protein structures that delivers strong codebook use, token diversity, and reconstruction while enabling from-scratch multimodal generation of plausible sequences and structures with 10x fewer parameters than ESM3.
Protein language models exhibit consistent depth inefficiency where most task-relevant computation occurs in a subset of layers, mirroring patterns in large language models.
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A-CODE: Fully Atomic Protein Co-Design with Unified Multimodal Diffusion
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Steerable Neural ODEs on Homogeneous Spaces
Steerable NODEs extend manifold neural ODEs by coupling base flow on homogeneous spaces with parallel transport of features in associated bundles, achieving G-equivariance under invariant conditions.
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General Multimodal Protein Design Enables DNA-Encoding of Chemistry
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Yeti: A compact protein structure tokenizer for reconstruction and multi-modal generation
Yeti is a compact tokenizer for protein structures that delivers strong codebook use, token diversity, and reconstruction while enabling from-scratch multimodal generation of plausible sequences and structures with 10x fewer parameters than ESM3.
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From Words to Amino Acids: Does the Curse of Depth Persist?
Protein language models exhibit consistent depth inefficiency where most task-relevant computation occurs in a subset of layers, mirroring patterns in large language models.