Sarah A. Altwaim , Isra M. Alsaady , Hattan S. Gattan , Mohammed H. Alruhaili , Aiah M. Khateb , Mai M. El-Daly , Amit Dubey , Vivek Dhar Dwivedi , Esam I. Azhar
{"title":"通过分子动力学模拟探索针对副隐孢子虫乳酸脱氢酶的芳香紫苏植物化学物质的抗原虫机制","authors":"Sarah A. Altwaim , Isra M. Alsaady , Hattan S. Gattan , Mohammed H. Alruhaili , Aiah M. Khateb , Mai M. El-Daly , Amit Dubey , Vivek Dhar Dwivedi , Esam I. Azhar","doi":"10.1016/j.abb.2024.110124","DOIUrl":null,"url":null,"abstract":"<div><p><em>Cryptosporidium parvum</em> (<em>C. parvum</em>), a protozoan parasite, is known to induce significant gastrointestinal disease in humans. Lactate dehydrogenase (LDH), a protein of <em>C. parvum</em>, has been identified as a potential therapeutic target for developing effective drugs against infection. This study utilized a computational drug discovery approach to identify potential drug molecules against the LDH protein of <em>C. parvum</em>. In the present investigation, we conducted a structure-based virtual screening of 55 phytochemicals from the <em>Syzygium aromaticum</em> (<em>S. aromaticum</em>). This process identified four phytochemicals, including Gallotannin 23, Eugeniin, Strictinin, and Ellagitannin, that demonstrated significant binding affinity and dynamic stability with LDH protein. Interestingly, these four compounds have been documented to possess antibacterial, antiviral, anti-inflammatory, and antioxidant properties. The docked complexes were simulated for 100 ns using Desmond to check the dynamic stability. Finally, the free binding energy was computed from the last 10ns MD trajectories. Gallotannin 23 and Ellagitannin exhibited considerable binding affinity and stability with the target protein among all four phytochemicals. These findings suggest that these predicted phytochemicals from <em>S. aromaticum</em> could be further explored as potential hit candidates for developing effective drugs against <em>C. parvum</em> infection. The in vitro and in vivo experimental validation is still required to confirm their efficacy and safety as LDH inhibitors.</p></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"760 ","pages":"Article 110124"},"PeriodicalIF":3.8000,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the anti-protozoal mechanisms of Syzygium aromaticum phytochemicals targeting Cryptosporidium parvum lactate dehydrogenase through molecular dynamics simulations\",\"authors\":\"Sarah A. Altwaim , Isra M. Alsaady , Hattan S. Gattan , Mohammed H. Alruhaili , Aiah M. Khateb , Mai M. El-Daly , Amit Dubey , Vivek Dhar Dwivedi , Esam I. Azhar\",\"doi\":\"10.1016/j.abb.2024.110124\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><em>Cryptosporidium parvum</em> (<em>C. parvum</em>), a protozoan parasite, is known to induce significant gastrointestinal disease in humans. Lactate dehydrogenase (LDH), a protein of <em>C. parvum</em>, has been identified as a potential therapeutic target for developing effective drugs against infection. This study utilized a computational drug discovery approach to identify potential drug molecules against the LDH protein of <em>C. parvum</em>. In the present investigation, we conducted a structure-based virtual screening of 55 phytochemicals from the <em>Syzygium aromaticum</em> (<em>S. aromaticum</em>). This process identified four phytochemicals, including Gallotannin 23, Eugeniin, Strictinin, and Ellagitannin, that demonstrated significant binding affinity and dynamic stability with LDH protein. Interestingly, these four compounds have been documented to possess antibacterial, antiviral, anti-inflammatory, and antioxidant properties. The docked complexes were simulated for 100 ns using Desmond to check the dynamic stability. Finally, the free binding energy was computed from the last 10ns MD trajectories. Gallotannin 23 and Ellagitannin exhibited considerable binding affinity and stability with the target protein among all four phytochemicals. These findings suggest that these predicted phytochemicals from <em>S. aromaticum</em> could be further explored as potential hit candidates for developing effective drugs against <em>C. parvum</em> infection. The in vitro and in vivo experimental validation is still required to confirm their efficacy and safety as LDH inhibitors.</p></div>\",\"PeriodicalId\":8174,\"journal\":{\"name\":\"Archives of biochemistry and biophysics\",\"volume\":\"760 \",\"pages\":\"Article 110124\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-08-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of biochemistry and biophysics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0003986124002467\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of biochemistry and biophysics","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0003986124002467","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Exploring the anti-protozoal mechanisms of Syzygium aromaticum phytochemicals targeting Cryptosporidium parvum lactate dehydrogenase through molecular dynamics simulations
Cryptosporidium parvum (C. parvum), a protozoan parasite, is known to induce significant gastrointestinal disease in humans. Lactate dehydrogenase (LDH), a protein of C. parvum, has been identified as a potential therapeutic target for developing effective drugs against infection. This study utilized a computational drug discovery approach to identify potential drug molecules against the LDH protein of C. parvum. In the present investigation, we conducted a structure-based virtual screening of 55 phytochemicals from the Syzygium aromaticum (S. aromaticum). This process identified four phytochemicals, including Gallotannin 23, Eugeniin, Strictinin, and Ellagitannin, that demonstrated significant binding affinity and dynamic stability with LDH protein. Interestingly, these four compounds have been documented to possess antibacterial, antiviral, anti-inflammatory, and antioxidant properties. The docked complexes were simulated for 100 ns using Desmond to check the dynamic stability. Finally, the free binding energy was computed from the last 10ns MD trajectories. Gallotannin 23 and Ellagitannin exhibited considerable binding affinity and stability with the target protein among all four phytochemicals. These findings suggest that these predicted phytochemicals from S. aromaticum could be further explored as potential hit candidates for developing effective drugs against C. parvum infection. The in vitro and in vivo experimental validation is still required to confirm their efficacy and safety as LDH inhibitors.
期刊介绍:
Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics.
Research Areas Include:
• Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing
• Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions
• Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.