arXiv:2608.31009cs.LG2026-08中稿 · EMNLP

用语言提示引导三维分子生成,提升药物设计效率。

Language-Informed Flow Matching for Trend-Guided Structure-Based 3D Molecular Generation

论文配图:Language-Informed Flow Matching for Trend-Guided Structure-Based 3D Molecular Generation
图 1 · 摘自论文原文
  • 通过语言信息生成目标导向的分子结构中间表示
  • 在无额外微调下实现高化学有效性与结构合理性
  • 适合需要高效分子设计的药学研究者

基于结构的药物设计(SBDD)要求配体同时满足三维靶点亲和力与一维化学有效性。现有可控生成方法常依赖特定任务微调或采样阶段外部引导,增加成本且可能与动态的三维几何约束冲突。我们提出LiFT,一种基于流匹配的语言引导跨模态框架,支持从头设计与骨架跃迁中的趋势引导三维分子生成。LiFT采用“感知-演化-组装”代理生成目标感知的SMILES作为中间化学条件,由预训练化学基础模型提取连续语义先验。这些先验通过轻量级语义投影器与零初始化自适应归一化融入几何生成过程,实现稳定跨模态条件控制。我们进一步提出自条件解耦路由器(SCDR),根据ODE积分过程中中间结构状态调节速度场。在Cross-Docked2020上的实验表明,LiFT在无需额外生成器微调的情况下,实现了具有竞争力的分布匹配,同时提升药物化学指标并保持结构有效性。结果表明,语言衍生的化学先验可为三维分子生成提供有效趋势级指导。代码与发布资源见https://github.com/kasurl/LiFT。

原文摘要 · Abstract (English)

Structure-based drug design (SBDD) requires ligands that satisfy both 3D target affinity and 1D chemical validity. Existing controllable generation methods often rely on task-specific fine-tuning or externally imposed sampling-time guidance, adding cost and potentially conflicting with evolving 3D geometric constraints. We propose LiFT, a language-informed cross-modal framework built on Flow Matching for trend-guided 3D molecular generation across both de novo design and scaffold hopping. LiFT uses a "Sense-Evolve-Assemble" agent to generate target-aware SMILES as intermediate chemical conditions, from which a pre-trained chemical foundation model extracts continuous semantic priors. These priors are integrated into geometric generation through a lightweight semantic projector with zero-initialized adaptive normalization for stable cross-modal conditioning. We further introduce a Self-Conditioned Decoupled Router (SCDR), which modulates the velocity field according to intermediate structural states during ODE integration. Experiments on Cross-Docked2020 show that LiFT achieves competitive distribution matching while improving medicinal chemistry metrics and maintaining competitive structural validity under task-steering settings without additional generator fine-tuning. Our results suggest that language-derived chemical priors provide effective trend-level guidance for 3D molecular generation. Code and released artifacts are available at https://github.com/kasurl/LiFT.

分子生成流匹配语言引导药物设计

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