Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular docking
Aim. To carry out in silico screening of interactions of synthetic glucocorticoids with TRPM8.Materials and methods. Information on the structure of the ligands was obtained from the PubChem chemical database in sdf format. The TRPM8 protein model was downloaded from the AlphaFold Protein Structure...
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Siberian State Medical University (Tomsk)
2025-01-01
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| Series: | Бюллетень сибирской медицины |
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| Online Access: | https://bulletin.ssmu.ru/jour/article/view/5881 |
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| author | P. D. Timkin D. D. Kotelnikov E. A. Timofeev D. E. Naumov E. A. Borodin |
| author_facet | P. D. Timkin D. D. Kotelnikov E. A. Timofeev D. E. Naumov E. A. Borodin |
| author_sort | P. D. Timkin |
| collection | DOAJ |
| description | Aim. To carry out in silico screening of interactions of synthetic glucocorticoids with TRPM8.Materials and methods. Information on the structure of the ligands was obtained from the PubChem chemical database in sdf format. The TRPM8 protein model was downloaded from the AlphaFold Protein Structure Database (AlpahaFold ID: AF-Q7Z2QW). Prediction of molecular cavities and coordinates of their centers was carried out on the PrankWeb web server. Modeling of molecular interactions was carried out using AutoDock (generation of 100 epochs) and MOE (generation of 300 poses) software.Results. The study revealed that the ligands formed stable complexes with TRPM8, but all of them, except for beclomethasone dipropionate, did not interact with the Tyr745 amino acid residue (the key binding site for channel activation). Thus, it can be assumed that glucocorticoids are most likely inhibitors of this ion channel. Of all glucocorticoids, special attention was paid to prednisolone, flunisolide, and budesonide, since the results of molecular docking of these molecules using AutoDock and MOE showed comparable data.Conclusion. The results obtained provide an insight into the therapeutic potential of these drugs in terms of their use in the treatment of cold-induced airway hyperresponsiveness and also expand the potential for their personalized use in the treatment of bronchial asthma and COPD. |
| format | Article |
| id | doaj-art-e5e757d6e9d64649ad8e471a6b631970 |
| institution | Kabale University |
| issn | 1682-0363 1819-3684 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Siberian State Medical University (Tomsk) |
| record_format | Article |
| series | Бюллетень сибирской медицины |
| spelling | doaj-art-e5e757d6e9d64649ad8e471a6b6319702025-08-20T03:37:41ZengSiberian State Medical University (Tomsk)Бюллетень сибирской медицины1682-03631819-36842025-01-0123413614410.20538/1682-0363-2024-4-136-1443122Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular dockingP. D. Timkin0D. D. Kotelnikov1E. A. Timofeev2D. E. Naumov3E. A. Borodin4Amur State Medical AcademyFar Eastern State Agrarian UniversityAmur State Medical AcademyFar Eastern Scientific Center for Physiology and Pathology of RespirationAmur State Medical AcademyAim. To carry out in silico screening of interactions of synthetic glucocorticoids with TRPM8.Materials and methods. Information on the structure of the ligands was obtained from the PubChem chemical database in sdf format. The TRPM8 protein model was downloaded from the AlphaFold Protein Structure Database (AlpahaFold ID: AF-Q7Z2QW). Prediction of molecular cavities and coordinates of their centers was carried out on the PrankWeb web server. Modeling of molecular interactions was carried out using AutoDock (generation of 100 epochs) and MOE (generation of 300 poses) software.Results. The study revealed that the ligands formed stable complexes with TRPM8, but all of them, except for beclomethasone dipropionate, did not interact with the Tyr745 amino acid residue (the key binding site for channel activation). Thus, it can be assumed that glucocorticoids are most likely inhibitors of this ion channel. Of all glucocorticoids, special attention was paid to prednisolone, flunisolide, and budesonide, since the results of molecular docking of these molecules using AutoDock and MOE showed comparable data.Conclusion. The results obtained provide an insight into the therapeutic potential of these drugs in terms of their use in the treatment of cold-induced airway hyperresponsiveness and also expand the potential for their personalized use in the treatment of bronchial asthma and COPD.https://bulletin.ssmu.ru/jour/article/view/5881trpm8molecular dockingglucocorticoidsin silico |
| spellingShingle | P. D. Timkin D. D. Kotelnikov E. A. Timofeev D. E. Naumov E. A. Borodin Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular docking Бюллетень сибирской медицины trpm8 molecular docking glucocorticoids in silico |
| title | Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular docking |
| title_full | Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular docking |
| title_fullStr | Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular docking |
| title_full_unstemmed | Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular docking |
| title_short | Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular docking |
| title_sort | studying molecular interactions of synthetic glucocorticoids with trpm8 by molecular docking |
| topic | trpm8 molecular docking glucocorticoids in silico |
| url | https://bulletin.ssmu.ru/jour/article/view/5881 |
| work_keys_str_mv | AT pdtimkin studyingmolecularinteractionsofsyntheticglucocorticoidswithtrpm8bymoleculardocking AT ddkotelnikov studyingmolecularinteractionsofsyntheticglucocorticoidswithtrpm8bymoleculardocking AT eatimofeev studyingmolecularinteractionsofsyntheticglucocorticoidswithtrpm8bymoleculardocking AT denaumov studyingmolecularinteractionsofsyntheticglucocorticoidswithtrpm8bymoleculardocking AT eaborodin studyingmolecularinteractionsofsyntheticglucocorticoidswithtrpm8bymoleculardocking |