Construction of a QSAR Model Based on Flavonoids and Screening of Natural Pancreatic Lipase Inhibitors

文献类型： 外文期刊

第一作者： Yuan, Yutong

作者： Yuan, Yutong;Zhu, Zehui;Yang, Zichen;Li, Qing;Zhao, Liang;Zhao, Lei;Yuan, Yutong;Pan, Fei;Wang, Ou

作者机构：

关键词： pancreatic lipase; dietary flavonoids; quantitative structure-activity relationship; molecular simulation; molecular mechanics; generalized born surface area

期刊名称：NUTRIENTS （ 影响因子：5.9； 五年影响因子：6.6 ）

ISSN：

年卷期： 2023 年 15 卷 15 期

页码：

收录情况： SCI

摘要： Pancreatic lipase (PL) is a key hydrolase in lipid metabolism. Inhibition of PL activity can intervene in obesity, a global sub-health disease. The natural product is considered a good alternative to chemically synthesized drugs due to its advantages, such as low side effects. However, traditional experimental screening methods are labor-intensive and cost-consuming, and there is an urgent need to develop high-throughput screening methods for the discovery of anti-PL natural products. In this study, a high-throughput virtual screening process for anti-PL natural products is provided. Firstly, a predictable anti-PL natural product QSAR model (R-train(2) = 0.9444, R-test(2) = 0.8962) were developed using the artificial intelligence drug design software MolAIcal based on genetic algorithms and their conformational relationships. 1068 highly similar (FS > 0.8) natural products were rapidly enriched based on the structure-activity similarity principle, combined with the QSAR model and the ADMET model, for rapid prediction of a total of five potentially efficient anti-PL natural products (IC50pre < 2 & mu;M). Subsequently, molecular docking, molecular dynamics simulation, and MMGBSA free energy calculation were performed to not only reveal the interaction of candidate novel natural products with the amino acid residues of PL but also to validate the stability of these novel natural compounds bound to PL. In conclusion, this study greatly simplifies the screening and discovery of anti-PL natural products and accelerates the development of novel anti-obesity functional foods.

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