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GraphATT-DTA: Attention-Based Novel Representation of Interaction to Predict Drug-Target Binding Affinity

Drug-target binding affinity (DTA) prediction is an essential step in drug discovery. Drug-target protein binding occurs at specific regions between the protein and drug, rather than the entire protein and drug. However, existing deep-learning DTA prediction methods do not consider the interactions...

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Detalles Bibliográficos
Autores principales: Bae, Haelee, Nam, Hojung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855982/
https://www.ncbi.nlm.nih.gov/pubmed/36672575
http://dx.doi.org/10.3390/biomedicines11010067
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author Bae, Haelee
Nam, Hojung
author_facet Bae, Haelee
Nam, Hojung
author_sort Bae, Haelee
collection PubMed
description Drug-target binding affinity (DTA) prediction is an essential step in drug discovery. Drug-target protein binding occurs at specific regions between the protein and drug, rather than the entire protein and drug. However, existing deep-learning DTA prediction methods do not consider the interactions between drug substructures and protein sub-sequences. This work proposes GraphATT-DTA, a DTA prediction model that constructs the essential regions for determining interaction affinity between compounds and proteins, modeled with an attention mechanism for interpretability. We make the model consider the local-to-global interactions with the attention mechanism between compound and protein. As a result, GraphATT-DTA shows an improved prediction of DTA performance and interpretability compared with state-of-the-art models. The model is trained and evaluated with the Davis dataset, the human kinase dataset; an external evaluation is achieved with the independently proposed human kinase dataset from the BindingDB dataset.
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spelling pubmed-98559822023-01-21 GraphATT-DTA: Attention-Based Novel Representation of Interaction to Predict Drug-Target Binding Affinity Bae, Haelee Nam, Hojung Biomedicines Article Drug-target binding affinity (DTA) prediction is an essential step in drug discovery. Drug-target protein binding occurs at specific regions between the protein and drug, rather than the entire protein and drug. However, existing deep-learning DTA prediction methods do not consider the interactions between drug substructures and protein sub-sequences. This work proposes GraphATT-DTA, a DTA prediction model that constructs the essential regions for determining interaction affinity between compounds and proteins, modeled with an attention mechanism for interpretability. We make the model consider the local-to-global interactions with the attention mechanism between compound and protein. As a result, GraphATT-DTA shows an improved prediction of DTA performance and interpretability compared with state-of-the-art models. The model is trained and evaluated with the Davis dataset, the human kinase dataset; an external evaluation is achieved with the independently proposed human kinase dataset from the BindingDB dataset. MDPI 2022-12-27 /pmc/articles/PMC9855982/ /pubmed/36672575 http://dx.doi.org/10.3390/biomedicines11010067 Text en © 2022 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
Bae, Haelee
Nam, Hojung
GraphATT-DTA: Attention-Based Novel Representation of Interaction to Predict Drug-Target Binding Affinity
title GraphATT-DTA: Attention-Based Novel Representation of Interaction to Predict Drug-Target Binding Affinity
title_full GraphATT-DTA: Attention-Based Novel Representation of Interaction to Predict Drug-Target Binding Affinity
title_fullStr GraphATT-DTA: Attention-Based Novel Representation of Interaction to Predict Drug-Target Binding Affinity
title_full_unstemmed GraphATT-DTA: Attention-Based Novel Representation of Interaction to Predict Drug-Target Binding Affinity
title_short GraphATT-DTA: Attention-Based Novel Representation of Interaction to Predict Drug-Target Binding Affinity
title_sort graphatt-dta: attention-based novel representation of interaction to predict drug-target binding affinity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855982/
https://www.ncbi.nlm.nih.gov/pubmed/36672575
http://dx.doi.org/10.3390/biomedicines11010067
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