{"title":"用人工智能(AI)和分子动力学方法探索和设计天然产品中潜在的 SIRT2 抑制剂","authors":"Yangyang Ni, Juxia Bai, Yuqi Zhang, Haoran Qiao, Liqun Liang, Junfeng Wan, Yanyan Zhu, Haijing Cao, Huiyu Li, Qingjie Zhao","doi":"10.2174/0115701808288696240308052948","DOIUrl":null,"url":null,"abstract":"Background:: The histone deacetylase family of proteins, which includes the sirtuins, participates in a wide range of cellular processes, and is intimately involved in neurodegenerative illnesses. The research on sirtuins has garnered a lot of interest. However, there are currently no effective therapeutic drugs. Methods:: In order to explore the potential inhibitors of SIRTs, we first screened four potential lead compounds of SIRT2 in Traditional Chinese Medicine (TCM) for nervous disease using the Auto- Dock Vina method. Then, with Molecular Dynamics (MD) simulation method, we discovered how these inhibitors from Traditional Chinese herbal medicines affect this protein at the atomic level. Results and Discussion:: We found hydrophobic interactions between inhibitors and SIRT2 to be crucial. The small molecules have been found to have strong effect on the residues in the zincbinding domain, exhibiting relationship with the signaling pathway. Finally, based on the conformational characteristics and the MD properties of the four potential inhibitors in TCM, we have designed the new skeleton molecules according to the parameters of binding energy, fingerprint similarity, 3D similarity, and RO5, with AI method using MolAICal software. Conclusion:: We have proposed the candidate inhibitor of SIRT2. Our research has provided a new approach that can be used to explore potential inhibitors from TCM. This could potentially pave the way for the creation of effective medicines.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.2000,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring and Designing Potential Inhibitors of SIRT2 in Natural Products by Artificial Intelligence (AI) and Molecular Dynamics Methods\",\"authors\":\"Yangyang Ni, Juxia Bai, Yuqi Zhang, Haoran Qiao, Liqun Liang, Junfeng Wan, Yanyan Zhu, Haijing Cao, Huiyu Li, Qingjie Zhao\",\"doi\":\"10.2174/0115701808288696240308052948\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background:: The histone deacetylase family of proteins, which includes the sirtuins, participates in a wide range of cellular processes, and is intimately involved in neurodegenerative illnesses. The research on sirtuins has garnered a lot of interest. However, there are currently no effective therapeutic drugs. Methods:: In order to explore the potential inhibitors of SIRTs, we first screened four potential lead compounds of SIRT2 in Traditional Chinese Medicine (TCM) for nervous disease using the Auto- Dock Vina method. Then, with Molecular Dynamics (MD) simulation method, we discovered how these inhibitors from Traditional Chinese herbal medicines affect this protein at the atomic level. Results and Discussion:: We found hydrophobic interactions between inhibitors and SIRT2 to be crucial. The small molecules have been found to have strong effect on the residues in the zincbinding domain, exhibiting relationship with the signaling pathway. Finally, based on the conformational characteristics and the MD properties of the four potential inhibitors in TCM, we have designed the new skeleton molecules according to the parameters of binding energy, fingerprint similarity, 3D similarity, and RO5, with AI method using MolAICal software. Conclusion:: We have proposed the candidate inhibitor of SIRT2. Our research has provided a new approach that can be used to explore potential inhibitors from TCM. This could potentially pave the way for the creation of effective medicines.\",\"PeriodicalId\":18059,\"journal\":{\"name\":\"Letters in Drug Design & Discovery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2024-03-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Letters in Drug Design & Discovery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0115701808288696240308052948\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Letters in Drug Design & Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115701808288696240308052948","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Exploring and Designing Potential Inhibitors of SIRT2 in Natural Products by Artificial Intelligence (AI) and Molecular Dynamics Methods
Background:: The histone deacetylase family of proteins, which includes the sirtuins, participates in a wide range of cellular processes, and is intimately involved in neurodegenerative illnesses. The research on sirtuins has garnered a lot of interest. However, there are currently no effective therapeutic drugs. Methods:: In order to explore the potential inhibitors of SIRTs, we first screened four potential lead compounds of SIRT2 in Traditional Chinese Medicine (TCM) for nervous disease using the Auto- Dock Vina method. Then, with Molecular Dynamics (MD) simulation method, we discovered how these inhibitors from Traditional Chinese herbal medicines affect this protein at the atomic level. Results and Discussion:: We found hydrophobic interactions between inhibitors and SIRT2 to be crucial. The small molecules have been found to have strong effect on the residues in the zincbinding domain, exhibiting relationship with the signaling pathway. Finally, based on the conformational characteristics and the MD properties of the four potential inhibitors in TCM, we have designed the new skeleton molecules according to the parameters of binding energy, fingerprint similarity, 3D similarity, and RO5, with AI method using MolAICal software. Conclusion:: We have proposed the candidate inhibitor of SIRT2. Our research has provided a new approach that can be used to explore potential inhibitors from TCM. This could potentially pave the way for the creation of effective medicines.
期刊介绍:
Aims & Scope
Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.