Proteo-R1: Reasoning Foundation Models for De Novo Protein Design

• URL: http://arxiv.org/abs/2605.02937v1
• Date: Fri, 01 May 2026 06:52:27 GMT
• Title: Proteo-R1: Reasoning Foundation Models for De Novo Protein Design
• Abstract summary: We introduce bfProteo-R1, a reasoning-guided protein design framework.<n>It decouples emphmolecular understanding from emphgeometric generation.<n>Proteo-R1 achieves stable, interpretable, and modular integration of reasoning with state-of-the-art geometric generative models.
• Score: 129.2825640976092
• License: http://creativecommons.org/licenses/by/4.0/
• Abstract: Deep learning in \emph{de novo} protein design has achieved atomic-level fidelity. However, existing models remain largely non-deliberative: they directly synthesize molecular geometries without explicitly reasoning about which residues or interactions are functionally essential. As a result, design decisions are entangled with continuous sampling dynamics, limiting interpretability, controllability, and systematic reuse of biochemical knowledge. We introduce \textbf{Proteo-R1}, a reasoning-guided protein design framework that explicitly decouples \emph{molecular understanding} from \emph{geometric generation}. Proteo-R1 adopts a dual-expert architecture in which a multimodal large language model (MLLM) serves as an \emph{understanding expert}, analyzing protein sequences, structures, and textual context to identify key functional residues that govern binding and specificity. These residue-level decisions are then passed as hard constraints to a separate diffusion-based \emph{generation expert}, which performs conditional co-design while respecting the fixed interaction anchors. This factorization mirrors how human experts approach molecular engineering: first, reasoning about critical interactions, then optimizing geometry subject to those constraints. By operationalizing reasoning as explicit residue-level commitments rather than latent textual guidance, Proteo-R1 achieves stable, interpretable, and modular integration of LLM reasoning with state-of-the-art geometric generative models. Code, data, and demos are available at https://smiles724.github.io/r1/.

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