arXiv:2602.07415cs.LGcs.AI2026-02中稿 · ICLR被引 2

提出新方法统一建模分子中心与轴向手性,提升手性预测准确率。

Learning Molecular Chirality via Chiral Determinant Kernels

  • 用旋转变换不变的手性行列式核编码立体化学信息
  • 在轴向手性任务上平均准确率提升超7%
  • 适用于需要精确手性建模的药物设计与光谱预测

手性是决定化学与生物中立体选择性行为的基本分子特性。现有机器学习模型在捕捉手性时面临几何复杂性与传统表示缺乏显式立体化学编码的挑战。当前方法多局限于中心手性,依赖人工标签或有限3D编码,难以推广至轴向手性等复杂形式。本文提出ChiDeK(手性行列式核)框架,通过旋转变换不变的手性行列式核编码立体化学信息,并利用交叉注意力将局部手性中心信息融入全局分子表征,实现对中心与轴向手性的统一建模。为评估轴向手性,构建了新的电子圆二色性(ECD)与光学旋转(OR)预测基准。在四类任务中——包括R/S构型分类、对映体排序、ECD谱预测与OR预测——ChiDeK显著优于现有基线,尤其在轴向手性任务上平均准确率提升超过7%。

原文摘要 · Abstract (English)

Chirality is a fundamental molecular property that governs stereospecific behavior in chemistry and biology. Capturing chirality in machine learning models remains challenging due to the geometric complexity of stereochemical relationships and the limitations of traditional molecular representations that often lack explicit stereochemical encoding. Existing approaches to chiral molecular representation primarily focus on central chirality, relying on handcrafted stereochemical tags or limited 3D encodings, and thus fail to generalize to more complex forms such as axial chirality. In this work, we introduce ChiDeK (Chiral Determinant Kernels), a framework that systematically integrates stereogenic information into molecular representation learning. We propose the chiral determinant kernel to encode the SE(3)-invariant chirality matrix and employ cross-attention to integrate stereochemical information from local chiral centers into the global molecular representation. This design enables explicit modeling of chiral-related features within a unified architecture, capable of jointly encoding central and axial chirality. To support the evaluation of axial chirality, we construct a new benchmark for electronic circular dichroism (ECD) and optical rotation (OR) prediction. Across four tasks, including R/S configuration classification, enantiomer ranking, ECD spectrum prediction, and OR prediction, ChiDeK achieves substantial improvements over state-of-the-art baselines, most notably yielding over 7% higher accuracy on axially chiral tasks on average.

分子建模手性预测深度学习量子化学

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