论分子表示的局限性
On the limitations of molecular representations
Acer Blake, Charlotte M. Deane, Fergus Imrie
AI 速读 基于摘要
系统评估表明,当前最先进的分子嵌入模型在捕捉图结构、3D 形状和 ADMET 终点相似性方面并不优于指纹或理化描述符,而经典指纹本身也存在表示不唯一等实质局限。
cs.LG
查看原文摘要
Molecular representations such as fingerprints and learned embeddings play a central role in cheminformatics and small-molecule machine learning. They serve as the primary input for a diverse array of tasks, including clustering, dataset splitting, and virtual screening, yet their evaluation is often limited to downstream model performance on narrow benchmark tasks. We carried out a systematic investigation of the quality of molecular representations, finding that none of the state-of-the-art molecular embedding models capture graph structure, 3D shape, or ADMET endpoint similarity better than fingerprints or physicochemical descriptors. However, classical fingerprints also revealed their own material limitations. For example, we show that depending on the representation, between 225M and $\sim$4B molecules have non-unique representations in the 10.8B Enamine REAL database, with implications for virtual screening. Our findings provide an insight into the current limitations of molecular representations, outlining future research directions for the development of more robust encodings of small molecules.