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3D Infomax improves GNNs for Molecular Property Prediction (2110.04126v4)

Published 8 Oct 2021 in cs.LG, cs.AI, and q-bio.BM

Abstract: Molecular property prediction is one of the fastest-growing applications of deep learning with critical real-world impacts. Including 3D molecular structure as input to learned models improves their performance for many molecular tasks. However, this information is infeasible to compute at the scale required by several real-world applications. We propose pre-training a model to reason about the geometry of molecules given only their 2D molecular graphs. Using methods from self-supervised learning, we maximize the mutual information between 3D summary vectors and the representations of a Graph Neural Network (GNN) such that they contain latent 3D information. During fine-tuning on molecules with unknown geometry, the GNN still generates implicit 3D information and can use it to improve downstream tasks. We show that 3D pre-training provides significant improvements for a wide range of properties, such as a 22% average MAE reduction on eight quantum mechanical properties. Moreover, the learned representations can be effectively transferred between datasets in different molecular spaces.

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Authors (7)
  1. Hannes Stärk (20 papers)
  2. Dominique Beaini (27 papers)
  3. Gabriele Corso (17 papers)
  4. Prudencio Tossou (11 papers)
  5. Christian Dallago (5 papers)
  6. Stephan Günnemann (169 papers)
  7. Pietro Liò (270 papers)
Citations (185)

Summary

Molecular Property Prediction Enhanced by 3D Infomax Pre-training of GNNs

The paper "3D Infomax improves GNNs for Molecular Property Prediction" presents a sophisticated approach for improving molecular property prediction using Graph Neural Networks (GNNs). Molecular property prediction has critical applications across multiple domains such as drug discovery, material science, and quantum chemistry, necessitating the need for high-precision models. The authors address a significant bottleneck: the computational infeasibility of obtaining large-scale 3D molecular structures needed for effective downstream property prediction.

Methodology Overview

The cornerstone of this approach is the development of 3D Infomax, a method leveraging self-supervised learning (SSL) to impart implicit 3D knowledge into GNNs through pre-training. The method capitalizes on available 3D molecular datasets to learn 3D geometric reasoning from associated 2D molecular graphs, optimizing for the mutual information (MI) between 3D summary vectors and GNN representations. Notably, the pre-trained model retains the ability to deduce and use implicit 3D information for molecules lacking explicit geometric data during fine-tuning.

Key Results

The research demonstrates substantial effectiveness through various pre-training and fine-tuning experiments:

  • Performance Improvement: For quantum mechanical properties in the QM9 dataset, 3D Infomax achieved an average 22% reduction in Mean Absolute Error (MAE) compared to models without 3D information.
  • Generalization: The method showcased robust transfer capabilities across disparate molecular datasets, managing to enhance results despite stark differences in molecular size and composition between pre-training and fine-tuning phases.
  • Computational Efficiency: The approach allows swift inference with a single forward pass of the 2D model while encapsulating complex 3D interactions.

Theoretical and Practical Implications

Theoretically, this work extends the utility of SSL in molecular modeling by incorporating 3D geometric understanding, suggesting a unified representation space advantageous for various molecular tasks regardless of available dimensional data. Practically, it provides a path towards efficient and scalable molecular property predictions even when detailed molecular geometries are absent, which is often the case in real-world applications like drug screening and property analysis of new materials.

Speculation on Future Developments

This paper sets the foundation for several promising future avenues in AI within computational chemistry and materials science:

  • Integration with Conformer Generations: Further improvements may arise by integrating methods capable of predicting multiple molecular conformers, aligning with the direction introduced by the authors' exploration of leveraging multiple conformers in pre-training.
  • Extension to Higher Dimensional Features: Expanding the modeling to incorporate more complex features such as full electronic behavior representations could improve the applicability range to novel quantum mechanical challenges.
  • Alternative Graph Representations: Further exploration into alternative graph representations and architectural innovations can potentially yield deeper insights into the trade-offs between model interpretability and prediction fidelity.

In conclusion, 3D Infomax represents a significant contribution to the domain of molecular property prediction, particularly in scenarios where access to explicit 3D data is limited. It opens a pathway for leveraging extensive 2D datasets in a manner that implicitly harnesses 3D molecular characteristics, paving the way for continual advancements in predictive modeling in chemistry and beyond.