# Geometric Multi-color Message Passing Graph Neural Networks for Blood-brain Barrier Permeability Prediction

arXiv: https://arxiv.org/abs/2507.18926 · HTML: https://mlsanity.com/paper/2507.18926/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 10 of its 45 references that are in the map.
- First posted on arXiv 25 Jul 2025.

## Builds on (most cited first, 10 of 10)

- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [Neural Message Passing for Quantum Chemistry](https://mlsanity.com/paper/1704.01212/) (2017)
- [A Comprehensive Survey on Graph Neural Networks](https://mlsanity.com/paper/1901.00596/) (2019)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [Convolutional Networks on Graphs for Learning Molecular Fingerprints](https://mlsanity.com/paper/1509.09292/) (2015)
- [Molecular Graph Convolutions: Moving Beyond Fingerprints](https://mlsanity.com/paper/1603.00856/) (2016)
- [Learning Attributed Graph Representations with Communicative Message Passing Transformer](https://mlsanity.com/paper/2107.08773/) (2021)
- [Molecular geometric deep learning](https://mlsanity.com/paper/2306.15065/) (2023)
- [Molecular Property Prediction Based on Graph Structure Learning](https://mlsanity.com/paper/2312.16855/) (2023)

## Built on by (most cited first, 1 of 1)

- [MolGraphBench: A Benchmark of GNN Architectures for Molecular Regression Tasks](https://mlsanity.com/paper/2602.20573/) (2026)

## Abstract (arXiv)

Accurate prediction of blood-brain barrier permeability (BBBP) is essential for central nervous system (CNS) drug development. While graph neural networks (GNNs) have advanced molecular property prediction, they often rely on molecular topology and neglect the three-dimensional geometric information crucial for modeling transport mechanisms. This paper introduces the geometric multi-color message-passing graph neural network (GMC-MPNN), a novel framework that enhances standard message-passing architectures by explicitly incorporating atomic-level geometric features and long-range interactions. Our model constructs weighted colored subgraphs based on atom types to capture the spatial relationships and chemical context that govern BBB permeability. We evaluated GMC-MPNN on three benchmark datasets for both classification and regression tasks, using rigorous scaffold-based splitting to ensure a robust assessment of generalization. The results demonstrate that GMC-MPNN consistently outperforms existing state-of-the-art models, achieving superior performance in both classifying compounds as permeable/non-permeable (AUC-ROC of 0.947 and 0.9212) and in regressing continuous permeability values (RMSE of 0.5628, Pearson correlation of 0.6947). An ablation study further quantified the impact of specific atom-pair interactions, revealing that the model's predictive power derives from its ability to learn from both common and rare, but chemically significant, functional motifs. By integrating spatial geometry into the graph representation, GMC-MPNN sets a new performance benchmark and offers a more accurate and generalizable tool for drug discovery pipelines.