逆合成中顺序至关重要:通过反应中心引导的离散流匹配实现结构感知生成 / Order Matters in Retrosynthesis: Structure-aware Generation via Reaction-Center-Guided Discrete Flow Matching
1️⃣ 一句话总结
这篇论文提出了一种新的逆合成预测方法,通过将化学反应中心原子放在序列开头来引导模型学习,结合离散流匹配技术,用更少的数据和计算步骤实现了比传统方法更准确、更高效的分子合成路线预测。
Template-free retrosynthesis methods treat the task as black-box sequence generation, limiting learning efficiency, while semi-template approaches rely on rigid reaction libraries that constrain generalization. We address this gap with a key insight: atom ordering in neural representations matters. Building on this insight, we propose a structure-aware template-free framework that encodes the two-stage nature of chemical reactions as a positional inductive bias. By placing reaction center atoms at the sequence head, our method transforms implicit chemical knowledge into explicit positional patterns that the model can readily capture. The proposed RetroDiT backbone, a graph transformer with rotary position embeddings, exploits this ordering to prioritize chemically critical regions. Combined with discrete flow matching, our approach decouples training from sampling and enables generation in 20--50 steps versus 500 for prior diffusion methods. Our method achieves state-of-the-art performance on both USPTO-50k (61.2% top-1) and the large-scale USPTO-Full (51.3% top-1) with predicted reaction centers. With oracle centers, performance reaches 71.1% and 63.4% respectively, surpassing foundation models trained on 10 billion reactions while using orders of magnitude less data. Ablation studies further reveal that structural priors outperform brute-force scaling: a 280K-parameter model with proper ordering matches a 65M-parameter model without it.
逆合成中顺序至关重要:通过反应中心引导的离散流匹配实现结构感知生成 / Order Matters in Retrosynthesis: Structure-aware Generation via Reaction-Center-Guided Discrete Flow Matching
这篇论文提出了一种新的逆合成预测方法,通过将化学反应中心原子放在序列开头来引导模型学习,结合离散流匹配技术,用更少的数据和计算步骤实现了比传统方法更准确、更高效的分子合成路线预测。
源自 arXiv: 2602.13136