Mainal Furqan, Dachriyanus, Meri Susanti, Purnawan Pontana Putra, F. Wahyuni
{"title":"揭示加西尼酮-A 与乳腺癌中 her2 蛋白的相互作用:一项计算研究","authors":"Mainal Furqan, Dachriyanus, Meri Susanti, Purnawan Pontana Putra, F. Wahyuni","doi":"10.22159/ijap.2024.v16s1.24","DOIUrl":null,"url":null,"abstract":"Objective: One substance found in the leaves of Garcinia cowa Roxb that has anticancer properties is garcinisidone-A. The study aims to simulate the docking of garcinisidone-A (Gar-A), molecular dynamics, and predict the ADME by predicting the binding of the HER2 protein in breast cancer cells and developing new drug candidate options for cancer treatment, often starting with computational analysis. \nMethods: The research method involves computational utilization of pkCSM applications, Gar-A docking simulation with the HER2 protein using Gnina software version 1.0.2, and molecular dynamics conducted with GROMACS 2022.2 and CHARMMGUI applications. \nResults: Gar-A has a molecular weight of less than 500, a Log P value of greater than 5, a limited amount of water solubility, a low level of skin permeability, good intestinal permeability, and a Convolutional Neural Network (CNN) pose score on the HER2 protein of 0.6178. It also does not readily cross the blood-brain barrier, and total clearance values indicate rapid elimination via other excretory routes or enzyme metabolism. Gar-A is thought to have interactions with HER2. There are hydrogen bond interactions with amino acids Lys753 and Asp863, carbon-hydrogen bonds with amino acids Leu785, Ser783, Thr862, and alkyl bonds with amino acids Leu726, Leu852, and Ile767. The stability of the Gar-A-substrate interaction could have been more evident during 100 ns molecular dynamics simulation. \nConclusion: The physicochemical properties of Gar-A align with Lipinski's rule for drug candidates. ADME predictions indicate good intestinal permeability for Gar-A; however, it suggests it cannot penetrate the blood-brain barrier. The docking results reveal that Gar-A has a value close to one which indicates similar action to its natural ligand and molecular dynamics simulations that Gar-A is less stable. The results illustrate that Gar-A has the potential as a breast anticancer.","PeriodicalId":13737,"journal":{"name":"International Journal of Applied Pharmaceutics","volume":"32 7","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"UNRAVELLING THE INTERACTION BETWEEN GARCINISIDONE-A AND HER2 PROTEIN IN BREAST CANCER: A COMPUTATIONAL STUDY\",\"authors\":\"Mainal Furqan, Dachriyanus, Meri Susanti, Purnawan Pontana Putra, F. Wahyuni\",\"doi\":\"10.22159/ijap.2024.v16s1.24\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Objective: One substance found in the leaves of Garcinia cowa Roxb that has anticancer properties is garcinisidone-A. The study aims to simulate the docking of garcinisidone-A (Gar-A), molecular dynamics, and predict the ADME by predicting the binding of the HER2 protein in breast cancer cells and developing new drug candidate options for cancer treatment, often starting with computational analysis. \\nMethods: The research method involves computational utilization of pkCSM applications, Gar-A docking simulation with the HER2 protein using Gnina software version 1.0.2, and molecular dynamics conducted with GROMACS 2022.2 and CHARMMGUI applications. \\nResults: Gar-A has a molecular weight of less than 500, a Log P value of greater than 5, a limited amount of water solubility, a low level of skin permeability, good intestinal permeability, and a Convolutional Neural Network (CNN) pose score on the HER2 protein of 0.6178. It also does not readily cross the blood-brain barrier, and total clearance values indicate rapid elimination via other excretory routes or enzyme metabolism. Gar-A is thought to have interactions with HER2. There are hydrogen bond interactions with amino acids Lys753 and Asp863, carbon-hydrogen bonds with amino acids Leu785, Ser783, Thr862, and alkyl bonds with amino acids Leu726, Leu852, and Ile767. The stability of the Gar-A-substrate interaction could have been more evident during 100 ns molecular dynamics simulation. \\nConclusion: The physicochemical properties of Gar-A align with Lipinski's rule for drug candidates. ADME predictions indicate good intestinal permeability for Gar-A; however, it suggests it cannot penetrate the blood-brain barrier. The docking results reveal that Gar-A has a value close to one which indicates similar action to its natural ligand and molecular dynamics simulations that Gar-A is less stable. 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UNRAVELLING THE INTERACTION BETWEEN GARCINISIDONE-A AND HER2 PROTEIN IN BREAST CANCER: A COMPUTATIONAL STUDY
Objective: One substance found in the leaves of Garcinia cowa Roxb that has anticancer properties is garcinisidone-A. The study aims to simulate the docking of garcinisidone-A (Gar-A), molecular dynamics, and predict the ADME by predicting the binding of the HER2 protein in breast cancer cells and developing new drug candidate options for cancer treatment, often starting with computational analysis.
Methods: The research method involves computational utilization of pkCSM applications, Gar-A docking simulation with the HER2 protein using Gnina software version 1.0.2, and molecular dynamics conducted with GROMACS 2022.2 and CHARMMGUI applications.
Results: Gar-A has a molecular weight of less than 500, a Log P value of greater than 5, a limited amount of water solubility, a low level of skin permeability, good intestinal permeability, and a Convolutional Neural Network (CNN) pose score on the HER2 protein of 0.6178. It also does not readily cross the blood-brain barrier, and total clearance values indicate rapid elimination via other excretory routes or enzyme metabolism. Gar-A is thought to have interactions with HER2. There are hydrogen bond interactions with amino acids Lys753 and Asp863, carbon-hydrogen bonds with amino acids Leu785, Ser783, Thr862, and alkyl bonds with amino acids Leu726, Leu852, and Ile767. The stability of the Gar-A-substrate interaction could have been more evident during 100 ns molecular dynamics simulation.
Conclusion: The physicochemical properties of Gar-A align with Lipinski's rule for drug candidates. ADME predictions indicate good intestinal permeability for Gar-A; however, it suggests it cannot penetrate the blood-brain barrier. The docking results reveal that Gar-A has a value close to one which indicates similar action to its natural ligand and molecular dynamics simulations that Gar-A is less stable. The results illustrate that Gar-A has the potential as a breast anticancer.
期刊介绍:
International Journal of Applied Pharmaceutics (Int J App Pharm) is a peer-reviewed, bimonthly (onward March 2017) open access journal devoted to the excellence and research in the pure pharmaceutics. This Journal publishes original research work that contributes significantly to further the scientific knowledge in conventional dosage forms, formulation development and characterization, controlled and novel drug delivery, biopharmaceutics, pharmacokinetics, molecular drug design, polymer-based drug delivery, nanotechnology, nanocarrier based drug delivery, novel routes and modes of delivery; responsive delivery systems, prodrug design, development and characterization of the targeted drug delivery systems, ligand carrier interactions etc. However, the other areas which are related to the pharmaceutics are also entertained includes physical pharmacy and API (active pharmaceutical ingredients) analysis. The Journal publishes original research work either as a Original Article or as a Short Communication. Review Articles on a current topic in the said fields are also considered for publication in the Journal.