Analysis of Training and Seed Bias in Small Molecules Generated with a Conditional Graph-Based Variational Autoencoder─Insights for Practical AI-Driven Molecule Generation

The application of deep learning to generative molecule design has shown early promise for accelerating lead series development. However, questions remain concerning how factors like training, data set, and seed bias impact the technology's utility to medicinal and computational chemists. In th...

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Bibliographic Details
Published in:Journal of chemical information and modeling Vol. 62; no. 4; p. 801
Main Authors: Kang, Seung-Gu, Morrone, Joseph A, Weber, Jeffrey K, Cornell, Wendy D
Format: Journal Article
Language:English
Published: United States 28.02.2022
Subjects:
Artificial Intelligence
Models, Molecular
Receptors, Dopamine D2 - chemistry
ISSN:1549-960X, 1549-960X
Online Access:Get more information
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Summary:The application of deep learning to generative molecule design has shown early promise for accelerating lead series development. However, questions remain concerning how factors like training, data set, and seed bias impact the technology's utility to medicinal and computational chemists. In this work, we analyze the impact of seed and training bias on the output of an activity-conditioned graph-based variational autoencoder (VAE). Leveraging a massive, labeled data set corresponding to the dopamine D2 receptor, our graph-based generative model is shown to excel in producing desired conditioned activities and favorable unconditioned physical properties in generated molecules. We implement an activity-swapping method that allows for the activation, deactivation, or retention of activity of molecular seeds, and we apply independent deep learning classifiers to verify the generative results. Overall, we uncover relationships between noise, molecular seeds, and training set selection across a range of latent-space sampling procedures, providing important insights for practical AI-driven molecule generation.
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ISSN:1549-960X
1549-960X
DOI:10.1021/acs.jcim.1c01545