# Structural Hierarchy and Geometry in Molecular Representation Learning

arXiv: https://arxiv.org/abs/2608.29886 · HTML: https://mlsanity.com/paper/2608.29886/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 13 of its 18 references that are in the map.
- First posted on arXiv 30 Aug 2026.

## Builds on (most cited first, 13 of 13)

- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [Representation Learning with Contrastive Predictive Coding](https://mlsanity.com/paper/1807.03748/) (2018)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [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)
- [Poincar'e Embeddings for Learning Hierarchical Representations](https://mlsanity.com/paper/1705.08039/) (2017)
- [Learning Continuous Hierarchies in the Lorentz Model of Hyperbolic Geometry](https://mlsanity.com/paper/1806.03417/) (2018)
- [Hyperbolic Image-Text Representations](https://mlsanity.com/paper/2304.09172/) (2023)
- [Improving Molecular Contrastive Learning via Faulty Negative Mitigation and Decomposed Fragment Contrast](https://mlsanity.com/paper/2202.09346/) (2022)
- [Fragment-based Pretraining and Finetuning on Molecular Graphs](https://mlsanity.com/paper/2310.03274/) (2023)
- [Multi-channel learning for integrating structural hierarchies into context-dependent molecular representation](https://mlsanity.com/paper/2311.02798/) (2023)
- [Hyperbolic Molecular Representation Learning for Drug Repositioning](https://mlsanity.com/paper/2208.06361/) (2022)

## Abstract (arXiv)

Molecular self-supervised learning uses chemical structures to guide which molecular embeddings should be similar. We study whether explicitly encoding a molecule's Bemis-Murcko scaffold and using it to supervise the molecular embedding changes what the model learns. We further test whether this effect depends on the embedding geometry by comparing Euclidean and Lorentz contrastive objectives. Across two augmentation strengths, scaffold-supervised models consistently organize molecules according to both identical and structurally related scaffolds. The resulting embeddings also improve molecular property prediction on several tasks, while the exact gains depend on the predicted property. The effect of scaffold supervision on molecular organization is stronger under Lorentz objectives, but neither geometry provides a consistent overall advantage. These results show that explicitly teaching the relation between a molecule and its structural core can reliably shape the organization of molecular embedding space, while the extent of usefulness of this organization remains task dependent.