让分子片段在不同环境中自适应表达,提升模型对化学结构的理解能力。
BiScale-GTR: Fragment-Aware Graph Transformers for Multi-Scale Molecular Representation Learning

- 用图BPE构建可复用的片段词表,结合化学有效性过滤和递归分解。
- 通过原子到片段池化与门控融合,使相同片段在不同分子中获得上下文感知表示。
- 在多个基准上表现优异,且能解释关键化学结构与预测结果的关联。
片段级表示能自然捕捉分子中反复出现的子结构,并在不同分子间复用其学习到的表示。然而,仅靠共享片段标识无法完全描述该片段在特定分子中的具体表现,因为同一片段在不同的原子环境中有不同的化学行为。因此,有效的基于片段的分子学习需要既可复用又对局部原子环境敏感的表示。我们提出BiScale-GTR,一种围绕上下文感知共享片段标记构建的自监督分子表示框架。BiScale-GTR利用基于Weisfeiler-Lehman(WL)的片段身份、化学有效性过滤和递归未登录词(OOV)分解,构建可复用的图字节对编码(graph-BPE)词汇表。每个共享片段标记通过原子到片段池化和门控融合,与原子级GNN表示结合,使同一片段在不同分子环境中获得上下文依赖的表示。结构感知片段Transformer对这些原子接地的标记进行全局推理,捕获可复用的子结构身份、局部化学上下文及长程分子依赖关系。在MoleculeNet、PharmaBench和长程图基准上的实验表明,该方法在分类和回归任务中均表现出色。归因分析进一步显示,BiScale-GTR能够突出化学上有意义的重复基序,为分子结构与预测性质之间提供可解释的联系。
原文摘要 · Abstract (English)
Fragment-level representations provide a natural way to capture recurring molecular substructures and reuse their learned representations across molecules. However, a shared fragment identity alone may not fully describe how a fragment is instantiated in a particular molecule, since the same fragment can exhibit different chemical behavior depending on its surrounding atomic environment. Effective fragment-based molecular learning therefore requires representations that are both reusable across molecules and sensitive to local atomic context. We introduce BiScale-GTR, a self-supervised molecular representation framework built around context-grounded shared fragment tokens. BiScale-GTR constructs a reusable graph Byte Pair Encoding (graph-BPE) vocabulary using Weisfeiler-Lehman (WL)-based fragment identity, chemical validity filtering, and recursive out-of-vocabulary (OOV) decomposition. Each shared fragment token is then grounded with atom-level GNN representations through atom-to-fragment pooling and gated fusion, allowing the same fragment identity to acquire context-dependent representations in different molecular environments. A structure-aware fragment Transformer performs global reasoning over these atom-grounded tokens, capturing reusable substructure identity, local chemical context, and long-range molecular dependencies. Experiments on MoleculeNet, PharmaBench, and the Long Range Graph Benchmark demonstrate strong performance across classification and regression tasks. Attribution analysis further shows that BiScale-GTR highlights chemically meaningful recurring motifs, providing interpretable links between molecular structure and predicted properties.
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