# MolPLA: A Molecular Pretraining Framework for Learning Cores, R-Groups and their Linker Joints

arXiv: https://arxiv.org/abs/2401.16771 · HTML: https://mlsanity.com/paper/2401.16771/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 14 of its 43 references that are in the map.
- First posted on arXiv 30 Jan 2024.

## Builds on (most cited first, 14 of 14)

- [Inductive Representation Learning on Large Graphs](https://mlsanity.com/paper/1706.02216/) (2017)
- [Billion-scale similarity search with GPUs](https://mlsanity.com/paper/1702.08734/) (2017)
- [Conditional Generative Adversarial Nets](https://mlsanity.com/paper/1411.1784/) (2014)
- [Graph Contrastive Learning with Augmentations](https://mlsanity.com/paper/2010.13902/) (2020)
- [Strategies for Pre-training Graph Neural Networks](https://mlsanity.com/paper/1905.12265/) (2019)
- [InfoGraph: Unsupervised and Semi-supervised Graph-Level Representation Learning via Mutual Information Maximization](https://mlsanity.com/paper/1908.01000/) (2019)
- [GPT-GNN: Generative Pre-Training of Graph Neural Networks](https://mlsanity.com/paper/2006.15437/) (2020)
- [GEOM: Energy-annotated molecular conformations for property prediction and molecular generation](https://mlsanity.com/paper/2006.05531/) (2020)
- [Motif-based Graph Self-Supervised Learning for Molecular Property Prediction](https://mlsanity.com/paper/2110.00987/) (2021)
- [Learning to Extend Molecular Scaffolds with Structural Motifs](https://mlsanity.com/paper/2103.03864/) (2021)
- [Retrieval-based Controllable Molecule Generation](https://mlsanity.com/paper/2208.11126/) (2022)
- [Improving Molecular Contrastive Learning via Faulty Negative Mitigation and Decomposed Fragment Contrast](https://mlsanity.com/paper/2202.09346/) (2022)
- [DeepScaffold: a comprehensive tool for scaffold-based de novo drug discovery using deep learning](https://mlsanity.com/paper/1908.07209/) (2019)
- [Attention-wise masked graph contrastive learning for predicting molecular property](https://mlsanity.com/paper/2206.08262/) (2022)

## Abstract (arXiv)

Molecular core structures and R-groups are essential concepts in drug development. Integration of these concepts with conventional graph pre-training approaches can promote deeper understanding in molecules. We propose MolPLA, a novel pre-training framework that employs masked graph contrastive learning in understanding the underlying decomposable parts inmolecules that implicate their core structure and peripheral R-groups. Furthermore, we formulate an additional framework that grants MolPLA the ability to help chemists find replaceable R-groups in lead optimization scenarios. Experimental results on molecular property prediction show that MolPLA exhibits predictability comparable to current state-of-the-art models. Qualitative analysis implicate that MolPLA is capable of distinguishing core and R-group sub-structures, identifying decomposable regions in molecules and contributing to lead optimization scenarios by rationally suggesting R-group replacements given various query core templates. The code implementation for MolPLA and its pre-trained model checkpoint is available at https://github.com/dmis-lab/MolPLA