arXiv:2606.19377cs.LGcs.AI2026-06

用更小模型实现更快更准的蛋白质生成,适合酶设计。

Emyx: Fast and efficient all-atom protein generation

论文配图:Emyx: Fast and efficient all-atom protein generation
图 1 · 摘自论文原文
  • 基于轻量条件表示与流匹配,专注几何约束生成。
  • 仅用682小时训练,成功率超越更大模型。
  • 适合需要高结构多样性和几何准确性的酶设计。

计算酶设计需生成能支撑催化残基和配体的蛋白质,要求生成模型兼具几何精度与结构多样性。现有全原子生成模型沿用结构预测的昂贵架构,导致训练成本高且样本多样性受限。我们认为生成器无需复杂架构,因其仅依赖稀疏几何约束而非丰富的共进化信号。Emyx 是一个1.4亿参数的条件流匹配模型,将计算能力集中于标准Transformer块,以轻量级条件表示和稀疏连接替代复杂的嵌入堆叠。我们还推导出流匹配插值的精确重参数化,将其与EDM噪声水平框架对接,无需重新训练即可使用扩散模型的先进采样方法。尽管模型最小,Emyx 在严格评估下(要求全局折叠恢复、催化几何精度、结构新颖性、支架多样性与几何有效性)优于Proteína-Complexa和RFdiffusion3,训练仅耗时682 GPU小时,约为RFdiffusion3的1/4。

原文摘要 · Abstract (English)

Computational enzyme design requires generating proteins that scaffold catalytic residues and ligands, a task that demands both geometric accuracy and structural diversity from the underlying generative model. Current all-atom generators inherit expensive architectures from structure prediction, leading to high training costs and limited sample diversity. We argue that much of this complexity is unnecessary for generators, which condition on sparse geometric constraints rather than rich co-evolutionary signals. Emyx is a 140M-parameter conditional flow matching model that concentrates capacity within standard transformer blocks, replacing heavy embedding stacks with lightweight conditional representations and sparse connectivity. We additionally derive an exact reparametrisation of the flow matching interpolant into the EDM noise-level framework, bridging flow matching training efficiency with state-of-the-art sampling methods designed for diffusion models without retraining. Despite being the smallest model, Emyx outperforms both Proteína-Complexa and RFdiffusion3 against the AME enzyme design benchmark across success rate under strict evaluation requiring both global fold recovery and catalytic geometry accuracy, structural novelty, scaffold diversity, and geometric validity, while training in just $682$ GPU-hours, roughly $4\times$ less than RFdiffusion3.

蛋白质生成流匹配酶设计

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