# 3D Graph Contrastive Learning for Molecular Property Prediction

arXiv: https://arxiv.org/abs/2208.06360 · HTML: https://mlsanity.com/paper/2208.06360/

## Key facts

- Cited by 9 papers in the map (data through 14 Oct 2026).
- Builds on 29 of its 57 references that are in the map.
- First posted on arXiv 31 May 2022.

## Builds on (most cited first, 29 of 29)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Momentum Contrast for Unsupervised Visual Representation Learning](https://mlsanity.com/paper/1911.05722/) (2019)
- [Efficient Estimation of Word Representations in Vector Space](https://mlsanity.com/paper/1301.3781/) (2013)
- [Neural Message Passing for Quantum Chemistry](https://mlsanity.com/paper/1704.01212/) (2017)
- [Fast Graph Representation Learning with PyTorch Geometric](https://mlsanity.com/paper/1903.02428/) (2019)
- [Graph Contrastive Learning with Augmentations](https://mlsanity.com/paper/2010.13902/) (2020)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Strategies for Pre-training Graph Neural Networks](https://mlsanity.com/paper/1905.12265/) (2019)
- [SchNet: A continuous-filter convolutional neural network for modeling quantum interactions](https://mlsanity.com/paper/1706.08566/) (2017)
- [Directional Message Passing for Molecular Graphs](https://mlsanity.com/paper/2003.03123/) (2020)
- [Analyzing Learned Molecular Representations for Property Prediction](https://mlsanity.com/paper/1904.01561/) (2019)
- [ChemBERTa: Large-Scale Self-Supervised Pretraining for Molecular Property Prediction](https://mlsanity.com/paper/2010.09885/) (2020)
- [Pre-training Molecular Graph Representation with 3D Geometry](https://mlsanity.com/paper/2110.07728/) (2021)
- [ChemRL-GEM: Geometry Enhanced Molecular Representation Learning for Property Prediction](https://mlsanity.com/paper/2106.06130/) (2021)
- [Learning Gradient Fields for Molecular Conformation Generation](https://mlsanity.com/paper/2105.03902/) (2021)
- [3D Infomax improves GNNs for Molecular Property Prediction](https://mlsanity.com/paper/2110.04126/) (2021)
- [GeoMol: Torsional Geometric Generation of Molecular 3D Conformer Ensembles](https://mlsanity.com/paper/2106.07802/) (2021)
- [N-Gram Graph: Simple Unsupervised Representation for Graphs, with Applications to Molecules](https://mlsanity.com/paper/1806.09206/) (2018)
- [DIG: A Turnkey Library for Diving into Graph Deep Learning Research](https://mlsanity.com/paper/2103.12608/) (2021)
- [Molecular Property Prediction: A Multilevel Quantum Interactions Modeling Perspective](https://mlsanity.com/paper/1906.11081/) (2019)
- [MoCL: Data-driven Molecular Fingerprint via Knowledge-aware Contrastive Learning from Molecular Graph](https://mlsanity.com/paper/2106.04509/) (2021)
- [OrbNet: Deep Learning for Quantum Chemistry Using Symmetry-Adapted Atomic-Orbital Features](https://mlsanity.com/paper/2007.08026/) (2020)
- [Heterogeneous Molecular Graph Neural Networks for Predicting Molecule Properties](https://mlsanity.com/paper/2009.12710/) (2020)
- [Learning 3D Representations of Molecular Chirality with Invariance to Bond Rotations](https://mlsanity.com/paper/2110.04383/) (2021)
- [Learning Attributed Graph Representations with Communicative Message Passing Transformer](https://mlsanity.com/paper/2107.08773/) (2021)

## Built on by (most cited first, 9 of 9)

- [Pre-training with Fractional Denoising to Enhance Molecular Property Prediction](https://mlsanity.com/paper/2407.11086/) (2024)
- [Graph Neural Networks in Modern AI-aided Drug Discovery](https://mlsanity.com/paper/2506.06915/) (2025)
- [Impact of Domain Knowledge and Multi-Modality on Intelligent Molecular Property Prediction: A Systematic Survey](https://mlsanity.com/paper/2402.07249/) (2024)
- [WGFormer: An SE(3)-Transformer Driven by Wasserstein Gradient Flows for Molecular Ground-State Conformation Prediction](https://mlsanity.com/paper/2410.09795/) (2024)
- [Graph Multi-Similarity Learning for Molecular Property Prediction](https://mlsanity.com/paper/2401.17615/) (2024)
- [Implicit Neural Representations of Molecular Vector-Valued Functions](https://mlsanity.com/paper/2502.10848/) (2025)
- [Optimal message passing for molecular prediction is simple, attentive and spatial](https://mlsanity.com/paper/2509.10871/) (2025)
- [MolPaQ: Modular Quantum-Classical Patch Learning for Interpretable Molecular Generation](https://mlsanity.com/paper/2604.08575/) (2026)
- [ChemHyperMag: Physics-informed magnetic hypergraph learning improves molecular ADMET prediction](https://mlsanity.com/paper/2607.18332/) (2026)

## Abstract (arXiv)

Self-supervised learning (SSL) is a method that learns the data representation by utilizing supervision inherent in the data. This learning method is in the spotlight in the drug field, lacking annotated data due to time-consuming and expensive experiments. SSL using enormous unlabeled data has shown excellent performance for molecular property prediction, but a few issues exist. (1) Existing SSL models are large-scale; there is a limitation to implementing SSL where the computing resource is insufficient. (2) In most cases, they do not utilize 3D structural information for molecular representation learning. The activity of a drug is closely related to the structure of the drug molecule. Nevertheless, most current models do not use 3D information or use it partially. (3) Previous models that apply contrastive learning to molecules use the augmentation of permuting atoms and bonds. Therefore, molecules having different characteristics can be in the same positive samples. We propose a novel contrastive learning framework, small-scale 3D Graph Contrastive Learning (3DGCL) for molecular property prediction, to solve the above problems. 3DGCL learns the molecular representation by reflecting the molecule's structure through the pre-training process that does not change the semantics of the drug. Using only 1,128 samples for pre-train data and 1 million model parameters, we achieved the state-of-the-art or comparable performance in four regression benchmark datasets. Extensive experiments demonstrate that 3D structural information based on chemical knowledge is essential to molecular representation learning for property prediction.