High-throughput electronic property prediction of cyclic molecules with 3D-enhanced machine learning

利用三维增强机器学习技术对环状分子进行高通量电子性质预测

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Abstract

Complex organic molecules play a pivotal role in bioactive compounds and organic functional materials, yet existing molecular datasets lack structural diversity for such systems, limiting the generalizability of machine learning (ML) models. This study introduces a high-quality dataset, Ring Vault, comprising 201 546 cyclic molecules, including monocyclic, bicyclic, and tricyclic systems, spanning 11 non-metallic elements. This dataset covers a wide chemical space and provides a robust foundation for molecular property prediction. Leveraging quantum mechanical (QM) calculations on a subset (36 000 molecules), we trained three ML models (Graph Attention Network, Chemprop, and AIMNet2) to predict five key electronic properties: HOMO-LUMO gap, ionization potential (IP), electron affinity (EA), and redox potentials (E (ox), E (red)). The fine-tuned AIMNet2 model, incorporating 3D conformational information, outperformed 2D-based models, achieving R (2) values exceeding 0.95 and reducing mean absolute errors (MAEs) by over 30%. Principal component analysis (PCA) of AIMNet2 embeddings revealed intrinsic correlations between electronic properties and structural features, such as conjugation extent and functional group effects. This work establishes a robust framework for high-throughput screening and rational design of cyclic molecules, with applications spanning drug discovery, organic electronics, and energy materials. The dataset and methodology provide a foundation for exploring complex structure-property relationships and accelerating functional molecule discovery.

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