Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular docking
https://doi.org/10.20538/1682-0363-2024-4-136-144
Abstract
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.
About the Authors
P. D. Timkin
Amur State Medical Academy
Russian Federation
Russian Federation
101, Gorkogo Str., Blagoveshchensk, 675001
D. D. Kotelnikov
Far Eastern State Agrarian University
Russian Federation
Russian Federation
86, Politekhnicheskaya Str., Blagoveshchensk, 675005
E. A. Timofeev
Amur State Medical Academy
Russian Federation
Russian Federation
101, Gorkogo Str., Blagoveshchensk, 675001
D. E. Naumov
Far Eastern Scientific Center for Physiology and Pathology of Respiration
Russian Federation
Russian Federation
22, Kalinina Str., Blagoveshchensk, 675011
E. A. Borodin
Amur State Medical Academy
Russian Federation
Russian Federation
101, Gorkogo Str., Blagoveshchensk, 675001
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Review
For citations:
Timkin P.D., Kotelnikov D.D., Timofeev E.A., Naumov D.E., Borodin E.A. Studying molecular interactions of synthetic glucocorticoids with TRPM8 by molecular docking. Bulletin of Siberian Medicine. 2024;23(4):136-144. https://doi.org/10.20538/1682-0363-2024-4-136-144
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