Molecular modeling and molecular dynamics simulation studies on thyroid hormone receptor from Rattus norvegicus: role of conserved water molecules
| Autor: | Subrata Dasgupta, Utpal Adhikari, Soumita Mukherjee, Sujit S. Panja |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Molecular model
Molecular Conformation Molecular Dynamics Simulation 010402 general chemistry 01 natural sciences Catalysis DNA sequencing Inorganic Chemistry chemistry.chemical_compound Protein Domains 0103 physical sciences Animals Physical and Theoretical Chemistry Receptor Receptors Thyroid Hormone Thyroid hormone receptor 010304 chemical physics Chemistry Organic Chemistry Water Hydrogen Bonding DNA DNA-binding domain Ligand (biochemistry) Rats 0104 chemical sciences Computer Science Applications Computational Theory and Mathematics Nuclear receptor Biochemistry |
| Zdroj: | Journal of Molecular Modeling. 27 |
| ISSN: | 0948-5023 1610-2940 |
| DOI: | 10.1007/s00894-021-04740-1 |
| Popis: | Thyroid hormone receptor (THR) belongs to the nuclear receptor (NR) superfamily that is activated by binding of appropriate ligand molecules (thyroid hormones). These receptors directly bind to specific DNA sequences for gene expression, which is essential for metabolism, homeostasis, and the development of organisms, making it an important drug target. Extensive MD-simulation studies of triiodothyronine (T3) docked modeled rnTHRβ1 structures have indicated the presence of twelve conserved water molecules at the DNA-DBD (DNA binding domain) interface. The W1-W5 water centers have been involved in the recognition between the A-chain of DBD to C-chain of DNA, W6 and W7 mediated the interaction between A-chain of DBD and D-chain of DNA, W8 and W9 recognized the B-chain of DBD and C-chain of DNA, and W9-W12 centers conjugated the residues of B-chain of DBD to D-chain of DNA through hydrogen bonds. The conformation flexibility of Phe272 and Met313 residues in the absence of T3 at the LBD (ligand-binding domain) region have been observed and reported. |
| Databáze: | OpenAIRE |
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