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Cited by 19Computational Drug Discovery MethodsProtein Interaction Studies and Fluorescence Analysisvaccines and immunoinformatics approaches

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Caffeoyl malic acid is a potential dual inhibitor targeting TNFα/IL-4 evaluated by a combination strategy of network analysis-deep learning-molecular simulation

Wang, Yue, Qin, Dongya, Jin, Liang, Liang, Guizhao·2022·Computers in Biology and Medicine
DOI 10.1016/j.compbiomed.2022.105410
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Abstract

Atopic dermatitis (AD) is a common inflammatory skin disease involving multiple signaling pathways. One of the effective treatment strategies of AD is to develop a new drug capable of regulating the key therapeutic targets. Here we report the combination use of network analysis, deep learning, and molecular simulation for the identification of key therapeutic targets for AD and screening of potential multi-target drugs. From the TCM@Taiwan database, we identify a small molecule, namely caffeoyl malic acid (CMA), to inhibit the key therapeutic targets (TNFα and IL-4) for AD. CMA is further identified as a TNFα inhibitor by a deep learning model based on convolutional neural network. Molecular simulations demonstrate that CMA can stably bind to TNFα and IL-4, thereby producing diverse effects on the structural fluctuation, structural flexibility, looseness, and motion strength of each protein. Furthermore, conformation alignments reveal that CMA makes the distance between chain A and C of TNFα become wider and the slit between the two α helices of IL-4 get narrow obviously. CMA leads to the change of protein conformation, which hinders the formation of the protein-receptor complex. Collectively, our findings suggest that CMA is a potential dual TNFα/IL-4 inhibitor for the treatment of AD.

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Metadata

Authors
Wang, Y., Qin, D., Jin, L., & Liang, G.
Affiliations
Chongqing University (CN)
Corresponding author
Liang, Guizhao
ORCID
Venue
Computers in Biology and Medicine
Publisher
Elsevier BV
Published
2022-06
Volume
145
Pages
105410
ISSN
0010-4825 (ISSN-L)
DOI
10.1016/j.compbiomed.2022.105410
OpenAlex
W4220701619
Cited by
19
References
45
Citations by year
2026: 6 · 2025: 6 · 2024: 3 · 2023: 4
FWCI
1.76
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Computers in Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (32172196, 31771975)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
atopic dermatitis, TNF-α, IL-4, dual inhibitors, convolutional neural networks, protein-ligand binding, protein conformation, protein flexibility, traditional Chinese medicine
MeSH terms
Deep Learning, Dermatitis, Atopic, Humans, Malates, Tumor Necrosis Factor-alpha, Interleukin-4

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