Hybrid neural network approaches to predict drug–target binding affinity for drug repurposing: screening for potential leads for Alzheimer’s disease
Alzheimer’s disease (AD) is a neurodegenerative disease that primarily affects elderly individuals. Recent studies have found that sigma-1 receptor (S1R) agonists can maintain endoplasmic reticulum stress homeostasis, reduce neuronal apoptosis, and enhance mitochondrial function and autophagy, makin...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1227371/full |
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| author | Xialin Wu Xialin Wu Zhuojian Li Guanxing Chen Yiyang Yin Calvin Yu-Chian Chen Calvin Yu-Chian Chen Calvin Yu-Chian Chen |
| author_facet | Xialin Wu Xialin Wu Zhuojian Li Guanxing Chen Yiyang Yin Calvin Yu-Chian Chen Calvin Yu-Chian Chen Calvin Yu-Chian Chen |
| author_sort | Xialin Wu |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a neurodegenerative disease that primarily affects elderly individuals. Recent studies have found that sigma-1 receptor (S1R) agonists can maintain endoplasmic reticulum stress homeostasis, reduce neuronal apoptosis, and enhance mitochondrial function and autophagy, making S1R a target for AD therapy. Traditional experimental methods are costly and inefficient, and rapid and accurate prediction methods need to be developed, while drug repurposing provides new ways and options for AD treatment. In this paper, we propose HNNDTA, a hybrid neural network for drug–target affinity (DTA) prediction, to facilitate drug repurposing for AD treatment. The study combines protein–protein interaction (PPI) network analysis, the HNNDTA model, and molecular docking to identify potential leads for AD. The HNNDTA model was constructed using 13 drug encoding networks and 9 target encoding networks with 2506 FDA-approved drugs as the candidate drug library for S1R and related proteins. Seven potential drugs were identified using network pharmacology and DTA prediction results of the HNNDTA model. Molecular docking simulations were further performed using the AutoDock Vina tool to screen haloperidol and bromperidol as lead compounds for AD treatment. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation results indicated that both compounds had good pharmacokinetic properties and were virtually non-toxic. The study proposes a new approach to computer-aided drug design that is faster and more economical, and can improve hit rates for new drug compounds. The results of this study provide new lead compounds for AD treatment, which may be effective due to their multi-target action. HNNDTA is freely available at https://github.com/lizhj39/HNNDTA. |
| first_indexed | 2024-03-13T03:00:22Z |
| format | Article |
| id | doaj.art-35ec704a69354c169be85c0ff85ca84e |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-13T03:00:22Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-35ec704a69354c169be85c0ff85ca84e2023-06-27T14:46:53ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-06-011010.3389/fmolb.2023.12273711227371Hybrid neural network approaches to predict drug–target binding affinity for drug repurposing: screening for potential leads for Alzheimer’s diseaseXialin Wu0Xialin Wu1Zhuojian Li2Guanxing Chen3Yiyang Yin4Calvin Yu-Chian Chen5Calvin Yu-Chian Chen6Calvin Yu-Chian Chen7School of Computer Science and Technology, Guangdong University of Technology, Guangzhou, ChinaGuangzhou University of Chinese Medicine, Guangzhou, ChinaArtificial Intelligence Medical Research Center, School of Intelligent Systems Engineering, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaArtificial Intelligence Medical Research Center, School of Intelligent Systems Engineering, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaArtificial Intelligence Medical Research Center, School of Intelligent Systems Engineering, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaArtificial Intelligence Medical Research Center, School of Intelligent Systems Engineering, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, ChinaDepartment of Medical Research, China Medical University Hospital, Taichung, TaiwanDepartment of Bioinformatics and Medical Engineering, Asia University, Taichung, TaiwanAlzheimer’s disease (AD) is a neurodegenerative disease that primarily affects elderly individuals. Recent studies have found that sigma-1 receptor (S1R) agonists can maintain endoplasmic reticulum stress homeostasis, reduce neuronal apoptosis, and enhance mitochondrial function and autophagy, making S1R a target for AD therapy. Traditional experimental methods are costly and inefficient, and rapid and accurate prediction methods need to be developed, while drug repurposing provides new ways and options for AD treatment. In this paper, we propose HNNDTA, a hybrid neural network for drug–target affinity (DTA) prediction, to facilitate drug repurposing for AD treatment. The study combines protein–protein interaction (PPI) network analysis, the HNNDTA model, and molecular docking to identify potential leads for AD. The HNNDTA model was constructed using 13 drug encoding networks and 9 target encoding networks with 2506 FDA-approved drugs as the candidate drug library for S1R and related proteins. Seven potential drugs were identified using network pharmacology and DTA prediction results of the HNNDTA model. Molecular docking simulations were further performed using the AutoDock Vina tool to screen haloperidol and bromperidol as lead compounds for AD treatment. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation results indicated that both compounds had good pharmacokinetic properties and were virtually non-toxic. The study proposes a new approach to computer-aided drug design that is faster and more economical, and can improve hit rates for new drug compounds. The results of this study provide new lead compounds for AD treatment, which may be effective due to their multi-target action. HNNDTA is freely available at https://github.com/lizhj39/HNNDTA.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1227371/fullAlzheimer’s diseasedrug repurposinghybrid neural networkmolecular dockingsigma-1 receptor |
| spellingShingle | Xialin Wu Xialin Wu Zhuojian Li Guanxing Chen Yiyang Yin Calvin Yu-Chian Chen Calvin Yu-Chian Chen Calvin Yu-Chian Chen Hybrid neural network approaches to predict drug–target binding affinity for drug repurposing: screening for potential leads for Alzheimer’s disease Frontiers in Molecular Biosciences Alzheimer’s disease drug repurposing hybrid neural network molecular docking sigma-1 receptor |
| title | Hybrid neural network approaches to predict drug–target binding affinity for drug repurposing: screening for potential leads for Alzheimer’s disease |
| title_full | Hybrid neural network approaches to predict drug–target binding affinity for drug repurposing: screening for potential leads for Alzheimer’s disease |
| title_fullStr | Hybrid neural network approaches to predict drug–target binding affinity for drug repurposing: screening for potential leads for Alzheimer’s disease |
| title_full_unstemmed | Hybrid neural network approaches to predict drug–target binding affinity for drug repurposing: screening for potential leads for Alzheimer’s disease |
| title_short | Hybrid neural network approaches to predict drug–target binding affinity for drug repurposing: screening for potential leads for Alzheimer’s disease |
| title_sort | hybrid neural network approaches to predict drug target binding affinity for drug repurposing screening for potential leads for alzheimer s disease |
| topic | Alzheimer’s disease drug repurposing hybrid neural network molecular docking sigma-1 receptor |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1227371/full |
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