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In Silico Prediction of Metabolic Reaction Catalyzed by Human Aldehyde Oxidase

Aldehyde oxidase (AOX) plays an important role in drug metabolism. Human AOX (hAOX) is widely distributed in the body, and there are some differences between species. Currently, animal models cannot accurately predict the metabolism of hAOX. Therefore, more and more in silico models have been constr...

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Autores principales: Huang, Mengting, Zhu, Keyun, Wang, Yimeng, Lou, Chaofeng, Sun, Huimin, Li, Weihua, Tang, Yun, Liu, Guixia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059660/
https://www.ncbi.nlm.nih.gov/pubmed/36984889
http://dx.doi.org/10.3390/metabo13030449
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author Huang, Mengting
Zhu, Keyun
Wang, Yimeng
Lou, Chaofeng
Sun, Huimin
Li, Weihua
Tang, Yun
Liu, Guixia
author_facet Huang, Mengting
Zhu, Keyun
Wang, Yimeng
Lou, Chaofeng
Sun, Huimin
Li, Weihua
Tang, Yun
Liu, Guixia
author_sort Huang, Mengting
collection PubMed
description Aldehyde oxidase (AOX) plays an important role in drug metabolism. Human AOX (hAOX) is widely distributed in the body, and there are some differences between species. Currently, animal models cannot accurately predict the metabolism of hAOX. Therefore, more and more in silico models have been constructed for the prediction of the hAOX metabolism. These models are based on molecular docking and quantum chemistry theory, which are time-consuming and difficult to automate. Therefore, in this study, we compared traditional machine learning methods, graph convolutional neural network methods, and sequence-based methods with limited data, and proposed a ligand-based model for the metabolism prediction catalyzed by hAOX. Compared with the published models, our model achieved better performance (ACC = 0.91, F1 = 0.77). What’s more, we built a web server to predict the sites of metabolism (SOMs) for hAOX. In summary, this study provides a convenient and automatable model and builds a web server named Meta-hAOX for accelerating the drug design and optimization stage.
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spelling pubmed-100596602023-03-30 In Silico Prediction of Metabolic Reaction Catalyzed by Human Aldehyde Oxidase Huang, Mengting Zhu, Keyun Wang, Yimeng Lou, Chaofeng Sun, Huimin Li, Weihua Tang, Yun Liu, Guixia Metabolites Article Aldehyde oxidase (AOX) plays an important role in drug metabolism. Human AOX (hAOX) is widely distributed in the body, and there are some differences between species. Currently, animal models cannot accurately predict the metabolism of hAOX. Therefore, more and more in silico models have been constructed for the prediction of the hAOX metabolism. These models are based on molecular docking and quantum chemistry theory, which are time-consuming and difficult to automate. Therefore, in this study, we compared traditional machine learning methods, graph convolutional neural network methods, and sequence-based methods with limited data, and proposed a ligand-based model for the metabolism prediction catalyzed by hAOX. Compared with the published models, our model achieved better performance (ACC = 0.91, F1 = 0.77). What’s more, we built a web server to predict the sites of metabolism (SOMs) for hAOX. In summary, this study provides a convenient and automatable model and builds a web server named Meta-hAOX for accelerating the drug design and optimization stage. MDPI 2023-03-19 /pmc/articles/PMC10059660/ /pubmed/36984889 http://dx.doi.org/10.3390/metabo13030449 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Mengting
Zhu, Keyun
Wang, Yimeng
Lou, Chaofeng
Sun, Huimin
Li, Weihua
Tang, Yun
Liu, Guixia
In Silico Prediction of Metabolic Reaction Catalyzed by Human Aldehyde Oxidase
title In Silico Prediction of Metabolic Reaction Catalyzed by Human Aldehyde Oxidase
title_full In Silico Prediction of Metabolic Reaction Catalyzed by Human Aldehyde Oxidase
title_fullStr In Silico Prediction of Metabolic Reaction Catalyzed by Human Aldehyde Oxidase
title_full_unstemmed In Silico Prediction of Metabolic Reaction Catalyzed by Human Aldehyde Oxidase
title_short In Silico Prediction of Metabolic Reaction Catalyzed by Human Aldehyde Oxidase
title_sort in silico prediction of metabolic reaction catalyzed by human aldehyde oxidase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059660/
https://www.ncbi.nlm.nih.gov/pubmed/36984889
http://dx.doi.org/10.3390/metabo13030449
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