arXiv:2608.06259cs.LG2026-08

用对比学习建模反应转化结构,提升产率预测精度。

RxnCLF: Contrastive Transformation-Aware Reaction Foundation Model for Improved Reactivity Prediction

论文配图:RxnCLF: Contrastive Transformation-Aware Reaction Foundation Model for Improved Reactivity Prediction
图 1 · 摘自论文原文
  • 基于凝聚反应图统一反应物与产物信息,显式捕捉转化结构。
  • 在170万条反应上预训练,多任务验证中R2显著优于基线。
  • 适合需要化学可解释性的反应预测与优化场景。

反应产率预测因标注数据稀缺且反应空间组合爆炸、分布稀疏而困难,现有基于字符串、指纹或图的编码方式仅部分捕捉化学转化,难以处理复杂底物。本文提出反应对比学习基础模型RxnCLF,构建于凝聚反应图(CRG)之上,将反应物与产物信息统一为单一图结构,使模型能学习显式且丰富的转化结构。在170万条Pistachio反应上预训练后,RxnCLF获得紧凑连续的潜在空间,同时捕获反应中心特征与侧链上下文,具备转化感知与化学可解释性。在多个产率预测基准测试中(包括Buchwald-Hartwig、Pd催化BH偶联及专有HTE C-N偶联与酰胺形成数据集)微调后,其表现持续优于图与序列基线,显著提升R²,整体性能最优。结果表明,基于CRG的RxnCLF具有作为可扩展反应基础模型的潜力,可泛化至更广反应空间,支持区域选择性、对映选择性预测及反应条件优化等下游任务。

原文摘要 · Abstract (English)

Reaction yield prediction remains challenging because labeled data are scarce and reaction space is both combinatorially large and sparsely populated, limiting the generalization of existing reaction representations. String-, fingerprint-, and graph-based reaction encodings only partially capture chemical transformations, making accurate prediction difficult for reactions with complex substrates. We propose reaction contrastive learning foundation (RxnCLF), a self-supervised contrastive framework for reaction representation learning. RxnCLF is built on a condensed reaction graph (CRG) that unifies reactant and product information into a single graph, enabling the model to learn explicit and enriched transformation structure rather than disconnected graphs. Pretrained on 1.7 million Pistachio reactions, RxnCLF learns a compact and continuous latent space that captures both reaction-center features and broader side chain contexts, making it transformation-aware and chemically interpretable. Fine-tuned on multiple yield prediction benchmarks, including Buchwald-Hartwig, Pd-catalyzed BH coupling, and proprietary HTE C-N coupling and amide formation datasets, RxnCLF consistently outperforms graph and sequence-based baselines, improving R2 and achieving the best performance overall. Our results highlight the promise of CRG-based RxnCLF as a scalable reaction foundation model, with the potential to generalize across broader reaction spaces and support diverse downstream reaction informatics tasks, including regioselectivity prediction, enantioselectivity prediction, and reaction condition optimization.

反应预测对比学习凝聚图基础模型

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