BOOM: Benchmarking Out-Of-distribution Molecular Property Predictions of Machine Learning Models

Fuente: arXiv
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Main Authors: Antoniuk, Evan R., Zaman, Shehtab, Ben-Nun, Tal, Li, Peggy, Diffenderfer, James, Sahin, Busra, Smolenski, Obadiah, Hsu, Tim, Hiszpanski, Anna M., Chiu, Kenneth, Kailkhura, Bhavya, Van Essen, Brian
Format: Preprint
Published: 2025
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author Antoniuk, Evan R.
Zaman, Shehtab
Ben-Nun, Tal
Li, Peggy
Diffenderfer, James
Sahin, Busra
Smolenski, Obadiah
Hsu, Tim
Hiszpanski, Anna M.
Chiu, Kenneth
Kailkhura, Bhavya
Van Essen, Brian
author_facet Antoniuk, Evan R.
Zaman, Shehtab
Ben-Nun, Tal
Li, Peggy
Diffenderfer, James
Sahin, Busra
Smolenski, Obadiah
Hsu, Tim
Hiszpanski, Anna M.
Chiu, Kenneth
Kailkhura, Bhavya
Van Essen, Brian
contents Data-driven molecular discovery leverages artificial intelligence/machine learning (AI/ML) and generative modeling to filter and design novel molecules. Discovering novel molecules requires accurate out-of-distribution (OOD) predictions, but ML models struggle to generalize OOD. Currently, no systematic benchmarks exist for molecular OOD prediction tasks. We present $\mathbf{BOOM}$, $\mathbf{b}$enchmarks for $\mathbf{o}$ut-$\mathbf{o}$f-distribution $\mathbf{m}$olecular property predictions: a chemically-informed benchmark for OOD performance on common molecular property prediction tasks. We evaluate over 150 model-task combinations to benchmark deep learning models on OOD performance. Overall, we find that no existing model achieves strong generalization across all tasks: even the top-performing model exhibited an average OOD error 3x higher than in-distribution. Current chemical foundation models do not show strong OOD extrapolation, while models with high inductive bias can perform well on OOD tasks with simple, specific properties. We perform extensive ablation experiments, highlighting how data generation, pre-training, hyperparameter optimization, model architecture, and molecular representation impact OOD performance. Developing models with strong OOD generalization is a new frontier challenge in chemical ML. This open-source benchmark is available at https://github.com/FLASK-LLNL/BOOM
format Preprint
id arxiv_https___arxiv_org_abs_2505_01912
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle BOOM: Benchmarking Out-Of-distribution Molecular Property Predictions of Machine Learning Models
Antoniuk, Evan R.
Zaman, Shehtab
Ben-Nun, Tal
Li, Peggy
Diffenderfer, James
Sahin, Busra
Smolenski, Obadiah
Hsu, Tim
Hiszpanski, Anna M.
Chiu, Kenneth
Kailkhura, Bhavya
Van Essen, Brian
Machine Learning
Materials Science
Artificial Intelligence
Data-driven molecular discovery leverages artificial intelligence/machine learning (AI/ML) and generative modeling to filter and design novel molecules. Discovering novel molecules requires accurate out-of-distribution (OOD) predictions, but ML models struggle to generalize OOD. Currently, no systematic benchmarks exist for molecular OOD prediction tasks. We present $\mathbf{BOOM}$, $\mathbf{b}$enchmarks for $\mathbf{o}$ut-$\mathbf{o}$f-distribution $\mathbf{m}$olecular property predictions: a chemically-informed benchmark for OOD performance on common molecular property prediction tasks. We evaluate over 150 model-task combinations to benchmark deep learning models on OOD performance. Overall, we find that no existing model achieves strong generalization across all tasks: even the top-performing model exhibited an average OOD error 3x higher than in-distribution. Current chemical foundation models do not show strong OOD extrapolation, while models with high inductive bias can perform well on OOD tasks with simple, specific properties. We perform extensive ablation experiments, highlighting how data generation, pre-training, hyperparameter optimization, model architecture, and molecular representation impact OOD performance. Developing models with strong OOD generalization is a new frontier challenge in chemical ML. This open-source benchmark is available at https://github.com/FLASK-LLNL/BOOM
title BOOM: Benchmarking Out-Of-distribution Molecular Property Predictions of Machine Learning Models
topic Machine Learning
Materials Science
Artificial Intelligence
url https://arxiv.org/abs/2505.01912