arXiv:2410.02082cs.LGq-bio.QM2024-10被引 2

用官能团信息增强分子表示,提升模型对化学结构的理解能力。

FARM: Enhancing Molecular Representations with Functional Group Awareness

  • 在SMILES和图结构中注入原子级官能团标注,融合化学知识。
  • 在MoleculeNet上8项任务达顶尖水平,光稳定性预测表现优异。
  • 适合药物发现与功能材料设计,支持跨领域迁移学习。

我们提出功能团感知的小分子基础模型FARM,旨在弥合SMILES、自然语言与分子图之间的差距。FARM在原子级别引入官能团(FG)注释,生成富含官能团信息的增强型SMILES和官能团图。前者通过标识每个原子所属官能团丰富了化学上下文,后者以官能团连接关系表征分子拓扑。该表示法将化学先验知识融入SMILES,扩展有效分子词汇,更适配Transformer模型且接近自然语言结构。FARM从两个互补视角联合学习:基于增强型SMILES的掩码语言建模捕捉原子级特征,图神经网络建模官能团间的高级连接结构;再通过对比学习对齐两者至统一嵌入空间,确保原子细节与官能团结构共同表征。在MoleculeNet基准测试中,FARM在13项任务中有8项达到当前最优性能;在量子力学性质的光稳定性数据集上也验证了其泛化能力。结果表明,FARM显著提升了分子表示学习效果,支持药物研发与材料科学中的强迁移学习,并推动其在制药与功能材料设计中的广泛应用。

原文摘要 · Abstract (English)

We introduce Functional Group-Aware Representations for Small Molecules (FARM), a novel foundation model designed to bridge the gap between SMILES, natural language, and molecular graphs. The key idea behind FARM is the incorporation of functional group (FG) annotations at the atomic level, enabling both FG-enhanced SMILES and FG graphs. In this representation, SMILES strings are enriched with functional group information that identifies the group membership of each atom, while the FG graph captures molecular structure by representing how functional groups are connected. This tokenization injects chemical knowledge into SMILES and expands the effective molecular vocabulary, making the representation more suitable for Transformer-based models and more aligned with natural language structure. FARM learns molecular representations from two complementary perspectives to jointly encode functional and structural information. Masked language modeling on FG-enhanced SMILES captures atom-level features enriched with functional context, while graph neural networks model higher-level molecular topology through functional group connectivity. Contrastive learning is then used to align these two views into a unified embedding space, ensuring that both atom-level detail and functional group structure are jointly represented. We evaluate FARM on the MoleculeNet benchmark and achieve state-of-the-art performance on 8 out of 13 tasks. We further validate its generalization ability on a photostability dataset for quantum mechanical properties. These results demonstrate that FARM improves molecular representation learning, supports strong transfer learning across drug discovery and materials science, and enables broad applications in pharmaceutical research and functional material design.

分子表示官能团图神经网络迁移学习

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