用连续潜空间轨迹建模化学反应,让预测过程可解释、可诊断。
Driving Reaction Trajectories via Latent Flow Matching
- 将反应视为从反应物到产物的连续潜变量路径,直接从标准数据对中学习动态
- 在USPTO基准上达到顶尖性能,且能定位错误模式并提升可靠性
- 无需机理标注,可提供不确定性信号,适合高通量药物发现场景
近期反应预测研究在标准基准(如USPTO)上已接近饱和精度,但主流模型多将任务视为从反应物到产物的一次性映射,难以揭示反应过程。现有步骤生成方法常依赖特定机理监督、离散符号操作和高计算开销。本文提出LatentRxnFlow,一种基于条件流匹配的新范式,将反应建模为以热力学产物状态为锚点的连续潜空间轨迹。该方法直接从标准反应物-产物对中学习时间依赖的潜变量动态,无需机理标注或中间产物标签。尽管在USPTO基准上实现最先进性能,更重要的是,其连续形式暴露了完整生成轨迹,支持难以通过离散或一次性模型实现的轨迹级诊断。我们展示潜轨迹分析可用于定位与表征失败模式,并通过门控推理缓解部分错误。此外,学习轨迹的几何特性提供了内在的可信度不确定性信号,有助于优先处理可预测反应,标记模糊案例以进一步验证。总体而言,LatentRxnFlow结合了强预测准确率与更好的透明性、可诊断性和不确定性感知能力,推动反应预测向高通量发现工作流中的可信部署迈进。
原文摘要 · Abstract (English)
Recent advances in reaction prediction have achieved near-saturated accuracy on standard benchmarks (e.g., USPTO), yet most state-of-the-art models formulate the task as a one-shot mapping from reactants to products, offering limited insight into the underlying reaction process. Procedural alternatives introduce stepwise generation but often rely on mechanism-specific supervision, discrete symbolic edits, and computationally expensive inference. In this work, we propose LatentRxnFlow, a new reaction prediction paradigm that models reactions as continuous latent trajectories anchored at the thermodynamic product state. Built on Conditional Flow Matching, our approach learns time-dependent latent dynamics directly from standard reactant-product pairs, without requiring mechanistic annotations or curated intermediate labels. While LatentRxnFlow achieves state-of-the-art performance on USPTO benchmarks, more importantly, the continuous formulation exposes the full generative trajectory, enabling trajectory-level diagnostics that are difficult to realize with discrete or one-shot models. We show that latent trajectory analysis allows us to localize and characterize failure modes and to mitigate certain errors via gated inference. Furthermore, geometric properties of the learned trajectories provide an intrinsic signal of epistemic uncertainty, helping prioritize reliably predictable reaction outcomes and flag ambiguous cases for additional validation. Overall, LatentRxnFlow combines strong predictive accuracy with improved transparency, diagnosability, and uncertainty awareness, moving reaction prediction toward more trustworthy deployment in high-throughput discovery workflows.
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