From intuition to AI: evolution of small molecule representations in drug discovery

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McGibbon, Miles
Shave, Steven
Dong, Jie
Gao, Yumiao
Houston, Douglas R
Xie, Jiancong
Yang, Yuedong
Schwaller, Philippe
Blay, Vincent
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2023
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Abstract

Within drug discovery, the goal of AI scientists and cheminformaticians is to help identify molecular starting points that will develop into safe and efficacious drugs while reducing costs, time and failure rates. To achieve this goal, it is crucial to represent molecules in a digital format that makes them machine-readable and facilitates the accurate prediction of properties that drive decision-making. Over the years, molecular representations have evolved from intuitive and human-readable formats to bespoke numerical descriptors and fingerprints, and now to learned representations that capture patterns and salient features across vast chemical spaces. Among these, sequence-based and graph-based representations of small molecules have become highly popular. However, each approach has strengths and weaknesses across dimensions such as generality, computational cost, inversibility for generative applications and interpretability, which can be critical in informing practitioners' decisions. As the drug discovery landscape evolves, opportunities for innovation continue to emerge. These include the creation of molecular representations for high-value, low-data regimes, the distillation of broader biological and chemical knowledge into novel learned representations and the modeling of up-and-coming therapeutic modalities.

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Briefings in Bioinformatics

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25

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1

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© The Author(s) 2023. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Biochemistry and cell biology

Bioinformatics and computational biology

Genetics

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artificial intelligence

autoencoders

drug discovery

machine learning

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McGibbon, M; Shave, S; Dong, J; Gao, Y; Houston, DR; Xie, J; Yang, Y; Schwaller, P; Blay, V, From intuition to AI: evolution of small molecule representations in drug discovery, Briefings in Bioinformatics, 2023, 25 (1), pp. bbad422

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