用检索校准的协同机制,让小模型和大模型互补预测分子性质。
CoMPASS: Collaborative Molecular Property Prediction via Adaptive Small-Large Model Synergy

- 小模型为主,大模型提供可验证的化学推理作为修正依据。
- 在不确定区域提升预测准确率,高置信区避免错误干预。
- 适合需要可靠化学解释的药物研发与分子设计场景。
精准的分子性质预测需兼顾统计可靠性与化学逻辑。图神经网络可直接在标注实验数据上训练,但受限于训练数据覆盖范围;大语言模型能对比分子证据并生成化学推理,却难以作为独立的定量预测器。核心挑战在于确定何时以及多大程度应让大语言模型影响已校准的小模型。本文提出 CoMPASS,一种基于检索校准的小-大模型协作框架。CoMPASS 以图注意力网络(GAT)为预测主干,检索局部相关训练分子,将注意力驱动的证据提供给大语言模型,并通过一个关注一致性的门控机制,将其建议转化为有界修正。在六个分类和两个回归基准上,CoMPASS 在可纠正的不确定性区域提升了 GAT 的性能,同时在高置信区间限制了大语言模型的干预。消融实验证明,收益来自验证校准的检索与有界融合,而非仅靠提示工程。结果表明,生成式推理应通过基于证据、受控的修正来增强校准预测,而非直接替换输出。代码见 https://github.com/littlepeachs/CoMPASS。
原文摘要 · Abstract (English)
Accurate molecular property prediction requires both statistical reliability and chemical reasoning. Graph neural networks can be calibrated directly on labeled assays but remain limited by the coverage of their training data. Large language models (LLMs) can compare molecular evidence and articulate chemical rationales, yet are unreliable as standalone quantitative predictors. The central challenge is therefore to determine when an LLM should influence a calibrated model and by how much. Here we present CoMPASS, a retrieval-calibrated framework for small-large model collaboration. CoMPASS retains a graph attention network (GAT) as the predictive anchor, retrieves locally relevant training molecules, provides attention-grounded evidence to an LLM, and converts its proposal into a bounded correction through an agreement-aware gate. Across six classification and two regression benchmarks, CoMPASS improves the GAT anchor in regions of correctable uncertainty while limiting LLM intervention in high-confidence regimes. Ablations show that the gains arise from validation-calibrated retrieval and bounded fusion rather than prompting alone. These results suggest that generative reasoning should augment calibrated prediction through evidence-grounded, controlled corrections rather than direct output replacement. Code is available at https://github.com/littlepeachs/CoMPASS.
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