Uncertainty quantification with graph neural networks for efficient molecular design

Abstract Optimizing molecular design across expansive chemical spaces presents unique challenges, especially in maintaining predictive accuracy under domain shifts. This study integrates uncertainty quantification (UQ), directed message passing neural networks (D-MPNNs), and genetic algorithms (GAs)...

Full description

Saved in:
Bibliographic Details
Main Authors: Lung-Yi Chen, Yi-Pei Li
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58503-0
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Optimizing molecular design across expansive chemical spaces presents unique challenges, especially in maintaining predictive accuracy under domain shifts. This study integrates uncertainty quantification (UQ), directed message passing neural networks (D-MPNNs), and genetic algorithms (GAs) to address these challenges. We systematically evaluate whether UQ-enhanced D-MPNNs can effectively optimize broad, open-ended chemical spaces and identify the most effective implementation strategies. Using benchmarks from the Tartarus and GuacaMol platforms, our results show that UQ integration via probabilistic improvement optimization (PIO) enhances optimization success in most cases, supporting more reliable exploration of chemically diverse regions. In multi-objective tasks, PIO proves especially advantageous, balancing competing objectives and outperforming uncertainty-agnostic approaches. This work provides practical guidelines for integrating UQ in computational-aided molecular design (CAMD).
ISSN:2041-1723