2D-QSAR, Docking, Molecular dynamics simulations with the MM/GBSA approaches against Grave's disease and PTPN22
Graves' disease (GD) is an autoimmune condition that frequently causes hyperthyroidism and thyrotoxicosis. Protein tyrosine phosphatase, non-receptor type 22 (lymphoid) isoform 1 (PTPN22), is a promising therapeutic candidate for treating Graves' disease, rheumatoid arthritis, type 1 diab...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Institute for Researches and Community Services Universitas Muhammadiyah Palangkaraya
2023-08-01
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| Series: | Borneo Journal of Pharmacy |
| Subjects: | |
| Online Access: | https://journal.umpr.ac.id/index.php/bjop/article/view/4915 |
| _version_ | 1797693923147120640 |
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| author | Emmanuel Israel Edache Adamu Uzairu Paul Andrew Mamza Gideon Adamu Shallangwa |
| author_facet | Emmanuel Israel Edache Adamu Uzairu Paul Andrew Mamza Gideon Adamu Shallangwa |
| author_sort | Emmanuel Israel Edache |
| collection | DOAJ |
| description |
Graves' disease (GD) is an autoimmune condition that frequently causes hyperthyroidism and thyrotoxicosis. Protein tyrosine phosphatase, non-receptor type 22 (lymphoid) isoform 1 (PTPN22), is a promising therapeutic candidate for treating Graves' disease, rheumatoid arthritis, type 1 diabetes, and other autoimmune disorders. In this dataset, 31 molecular compounds and two standard drugs were optimized using the semi-empirical PM7 theory method via MOPAC v22.0.4 to reveal the key influencing factors contributing to their grave's disease inhibition activity and selectivity. Using QSARIN software, the acquired properties/descriptors were used to create a quantitative structural activities relationship (QSAR) model, and the similarities between the observed and predicted pIC50 values were examined. A molecular docking simulation study also uncovers non-covalent interactions between the investigated compounds and the receptors. The observed ligand-protein interactions with grave's disease proteins (PDB ID: 2XPG and 4QT5) and protein tyrosine phosphatase, non-receptor type 22 (lymphoid) isoform 1 (PTPN22) (PDB ID: 3BRH) were investigated. The pharmacokinetics (ADMET) properties were also investigated. Finally, molecular dynamics (MD) simulation and MMGBSA studies that demonstrated stable trajectory and molecular properties with a consistent interaction profile were used to validate the stability of the compounds in the complex with PTPN22.
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| first_indexed | 2024-03-12T02:50:39Z |
| format | Article |
| id | doaj.art-c7970fcd16f04082a9c88ee4041eb2c9 |
| institution | Directory Open Access Journal |
| issn | 2621-4814 |
| language | English |
| last_indexed | 2024-03-12T02:50:39Z |
| publishDate | 2023-08-01 |
| publisher | Institute for Researches and Community Services Universitas Muhammadiyah Palangkaraya |
| record_format | Article |
| series | Borneo Journal of Pharmacy |
| spelling | doaj.art-c7970fcd16f04082a9c88ee4041eb2c92023-09-04T03:44:28ZengInstitute for Researches and Community Services Universitas Muhammadiyah PalangkarayaBorneo Journal of Pharmacy2621-48142023-08-016310.33084/bjop.v6i3.49152D-QSAR, Docking, Molecular dynamics simulations with the MM/GBSA approaches against Grave's disease and PTPN22Emmanuel Israel Edache0Adamu Uzairu1Paul Andrew Mamza2Gideon Adamu Shallangwa3University of MaiduguriAhmadu Bello UniversityAhmadu Bello UniversityAhmadu Bello University Graves' disease (GD) is an autoimmune condition that frequently causes hyperthyroidism and thyrotoxicosis. Protein tyrosine phosphatase, non-receptor type 22 (lymphoid) isoform 1 (PTPN22), is a promising therapeutic candidate for treating Graves' disease, rheumatoid arthritis, type 1 diabetes, and other autoimmune disorders. In this dataset, 31 molecular compounds and two standard drugs were optimized using the semi-empirical PM7 theory method via MOPAC v22.0.4 to reveal the key influencing factors contributing to their grave's disease inhibition activity and selectivity. Using QSARIN software, the acquired properties/descriptors were used to create a quantitative structural activities relationship (QSAR) model, and the similarities between the observed and predicted pIC50 values were examined. A molecular docking simulation study also uncovers non-covalent interactions between the investigated compounds and the receptors. The observed ligand-protein interactions with grave's disease proteins (PDB ID: 2XPG and 4QT5) and protein tyrosine phosphatase, non-receptor type 22 (lymphoid) isoform 1 (PTPN22) (PDB ID: 3BRH) were investigated. The pharmacokinetics (ADMET) properties were also investigated. Finally, molecular dynamics (MD) simulation and MMGBSA studies that demonstrated stable trajectory and molecular properties with a consistent interaction profile were used to validate the stability of the compounds in the complex with PTPN22. https://journal.umpr.ac.id/index.php/bjop/article/view/4915Grave’s diseasePTPN22QSARDockingMolecular dynamics simulationsADMET |
| spellingShingle | Emmanuel Israel Edache Adamu Uzairu Paul Andrew Mamza Gideon Adamu Shallangwa 2D-QSAR, Docking, Molecular dynamics simulations with the MM/GBSA approaches against Grave's disease and PTPN22 Borneo Journal of Pharmacy Grave’s disease PTPN22 QSAR Docking Molecular dynamics simulations ADMET |
| title | 2D-QSAR, Docking, Molecular dynamics simulations with the MM/GBSA approaches against Grave's disease and PTPN22 |
| title_full | 2D-QSAR, Docking, Molecular dynamics simulations with the MM/GBSA approaches against Grave's disease and PTPN22 |
| title_fullStr | 2D-QSAR, Docking, Molecular dynamics simulations with the MM/GBSA approaches against Grave's disease and PTPN22 |
| title_full_unstemmed | 2D-QSAR, Docking, Molecular dynamics simulations with the MM/GBSA approaches against Grave's disease and PTPN22 |
| title_short | 2D-QSAR, Docking, Molecular dynamics simulations with the MM/GBSA approaches against Grave's disease and PTPN22 |
| title_sort | 2d qsar docking molecular dynamics simulations with the mm gbsa approaches against grave s disease and ptpn22 |
| topic | Grave’s disease PTPN22 QSAR Docking Molecular dynamics simulations ADMET |
| url | https://journal.umpr.ac.id/index.php/bjop/article/view/4915 |
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