arXiv:2503.06687cs.LGcond-mat.mtrl-sci2025-03被引 6

UniGenX统一生成序列、结构与功能,加速蛋白质、分子和材料设计。

UniGenX: a unified generative foundation model that couples sequence, structure and function to accelerate scientific design across proteins, molecules and materials

  • 联合优化序列与三维坐标,直接以功能为目标进行生成。
  • 在材料中实现436种满足三重约束的新晶体候选,11种为全新组合。
  • 适合需要功能导向生成的科研人员,尤其在生物、化学与材料领域。

自然系统中的功能源于一维序列形成三维结构并具备特定性质。然而现有生成模型存在关键缺陷:训练目标很少直接针对功能,离散序列与连续坐标分别优化,构象集合建模不足。我们提出UniGenX,一种统一的生成基础模型,通过在蛋白质、分子和材料中联合生成序列与坐标,并直接以功能与属性为目标,填补上述空白。UniGenX将异构输入表示为符号与数值标记的混合流,采用仅解码器的自回归变压器提供全局上下文,由条件扩散头生成受任务特定标记引导的数值场。除在结构预测任务上取得新SOTA外,该模型在跨域的功能感知生成中表现卓越:在材料领域,实现“矛盾”多属性条件生成,获得436个满足三重约束的晶格候选,其中11个为新组分;在化学领域,在五项属性目标及GEOM数据集上的构象集合生成上创下新基准;在生物学领域,蛋白质诱导契合建模成功率提升超过23倍(RMSD < 2 Å),并显著增强酶设计的EC条件生成能力。消融实验与跨域迁移验证了联合离散-连续训练的优势,确立UniGenX从预测到可控、功能感知生成的重大进展。

原文摘要 · Abstract (English)

Function in natural systems arises from one-dimensional sequences forming three-dimensional structures with specific properties. However, current generative models suffer from critical limitations: training objectives seldom target function directly, discrete sequences and continuous coordinates are optimized in isolation, and conformational ensembles are under-modeled. We present UniGenX, a unified generative foundation model that addresses these gaps by co-generating sequences and coordinates under direct functional and property objectives across proteins, molecules, and materials. UniGenX represents heterogeneous inputs as a mixed stream of symbolic and numeric tokens, where a decoder-only autoregressive transformer provides global context and a conditional diffusion head generates numeric fields steered by task-specific tokens. Besides the new high SOTAs on structure prediction tasks, the model demonstrates state-of-the-art or competitive performance for the function-aware generation across domains: in materials, it achieves "conflicted" multi-property conditional generation, yielding 436 crystal candidates meeting triple constraints, including 11 with novel compositions; in chemistry, it sets new benchmarks on five property targets and conformer ensemble generation on GEOM; and in biology, it improves success in modeling protein induced fit (RMSD < 2 Å) by over 23-fold and enhances EC-conditioned enzyme design. Ablation studies and cross-domain transfer substantiate the benefits of joint discrete-continuous training, establishing UniGenX as a significant advance from prediction to controllable, function-aware generation.

生成模型蛋白质设计材料生成功能导向

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