让化学分子推理可审计,模型用指纹嵌入生成有依据的解释。
Bolek: A Multimodal Language Model for Molecular Reasoning

- 将分子指纹嵌入文本解码器,实现结构驱动的语言推理。
- 在15个药物数据集上平均AUC提升至0.76,超越基线模型。
- 解释更可信:引用数值描述符频率高出10-100倍,与实际值高度一致。
分子性质模型日益用于高风险药物研发决策,但其输出难以审计:传统预测器仅返回分数无理由,而语言模型虽能生成流畅解释,却常缺乏对输入分子的扎实依据。我们提出Bolek,一个紧凑的多模态语言模型,通过将莫根指纹嵌入指令微调的文本解码器,使自然语言推理扎根于分子结构。Bolek在分子对齐任务(包括分子描述、RDKit描述符预测、子结构检测)及15个TDC二分类任务的下游推理上进行微调,采用以具体分子特征为锚点的合成思维链。在这些任务中,Bolek在所有指标上均优于Qwen3-4B-Instruct基线模型,且在思维链模式下15项中有13项表现更优,平均ROC/PR AUC从0.55提升至0.76。尽管模型规模不足TxGemma-9B-Chat的一半,仍能在15项任务中胜出13项。其解释更可信:每个思维链引用数值描述符次数比基线高10–100倍,且关键描述符如TPSA、MolLogP、MolWt的引用值与RDKit结果高度一致(斯皮尔曼相关系数0.87–0.91)。模型泛化能力超出训练集范围:在15个未见的TDC分类任务中,匹配了TxGemma在5项上的表现,并在3个保留回归任务上产生非平凡的相关性,尽管训练中从未接触过下游回归任务。结果表明,针对性的模态注入与可验证分子特征相关的推理监督,可生成紧凑且可审计的分子推理模型。
原文摘要 · Abstract (English)
Molecular property models increasingly support high-stakes drug-discovery decisions, but their outputs are often difficult to audit: classical predictors return scores without rationale, while language models can produce fluent explanations weakly grounded in the input molecule. We introduce Bolek, a compact multimodal language model that grounds natural-language reasoning in molecular structure by injecting a Morgan fingerprint embedding into an instruction-tuned text decoder. Bolek is fine-tuned on molecular alignment tasks, including molecule description, RDKit descriptor prediction, and substructure detection, and on downstream reasoning over 15 TDC binary classification tasks using synthetic chains-of-thought anchored in concrete molecular features. Across these tasks, Bolek outperforms its Qwen3-4B-Instruct base on all endpoints in yes/no mode and on 13 of 15 in chain-of-thought mode, raising mean ROC/PR AUC from 0.55 to 0.76. It also outperforms TxGemma-9B-Chat on 13 of 15 binary classification tasks despite being less than half its size. Bolek's explanations are more grounded than those of the baseline LLMs: it cites numerical descriptors 10-100x more often per chain-of-thought, and the cited values agree strongly with RDKit for key descriptors such as TPSA, MolLogP, and MolWt (Spearman rho = 0.87-0.91). Generalisation extends beyond the training panel: on 15 unseen TDC classification endpoints, Bolek matches TxGemma on five, and it produces non-trivial rank correlations on three held-out regression endpoints despite never seeing downstream regression during training. These results suggest that targeted modality injection and reasoning supervision tied to verifiable molecular features can yield compact, auditable molecular reasoning models.
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