Virtual Screening of GPX4 Agonists in the Active Ingredients of Artemisia Annua

YU Dayong; FU Siyu; WEN Zeyu; SONG Jia; SHI Liying

doi:10.6054/j.jscnun.2022086

Journal of South China Normal University (Natural Science Edition) > 2022 > 54(6): 59-67. > DOI: 10.6054/j.jscnun.2022086

YU Dayong, FU Siyu, WEN Zeyu, SONG Jia, SHI Liying. Virtual Screening of GPX4 Agonists in the Active Ingredients of Artemisia Annua[J]. Journal of South China Normal University (Natural Science Edition), 2022, 54(6): 59-67. DOI: 10.6054/j.jscnun.2022086

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Virtual Screening of GPX4 Agonists in the Active Ingredients of Artemisia Annua

College of Life and Health, Dalian University, Dalian 116622, China

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Received Date: June 10, 2021
Available Online: February 13, 2023

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Abstract

Glutathione peroxidase 4(GPX4) is a selenoprotein that can specifically catalyze the conversion of glutathione from lipid peroxides to lipid alcohols. Up-regulation of GPX4 expression plays an important role in inhibiting ferroptosis and related inflammation. In order to screen out the potential active small molecules that can activate glutathione peroxidase 4(GPX4) from Artemisia annua, 126 active small molecules of Artemisia annua were firstly retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform and 50 active small molecules of Artemisia annua were screened out according to drug-like properties. Further, 8 active small molecules of Artemisia annua were screened out through GPX4-ligand docking simulation and GPX4-ligand inte-raction pattern. Analysis and screening with GPX4-ligand free binding energy calculation found that artemisinin, patuletin and kaempferol acted similarly to the positive control 1d4(PKUMDL-LC-101-D03). Finally, molecular dynamics simulation was performed. The results showed that artemisinin, patuletin, kaempferol and the positive control 1d4 can form a stable complex with GPX4.
- GPX4,
- Ferroptosis,
- Artemisia annua,
- virtual screening,
- agonist

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