Investigation on critical structural motifs of ligands for triggering glucocorticoid receptor nuclear migration through molecular docking simulations
| Autor: | Soonmin Jang, Chiu-Hao Chen, Shih-Min Wang, Ya-Lin Liu, Feng-Yin Li |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular 0301 basic medicine Steric effects Stereochemistry Active Transport Cell Nucleus Molecular Conformation Molecular Dynamics Simulation Ligands Molecular Docking Simulation 03 medical and health sciences Receptors Glucocorticoid Glucocorticoid receptor Structural Biology Protein Interaction Domains and Motifs Structural motif Glucocorticoids Molecular Biology Transcription factor Ligand Chemistry General Medicine computer.file_format Protein Data Bank 030104 developmental biology Docking (molecular) Biophysics Hydrophobic and Hydrophilic Interactions computer Protein Binding |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 34:1214-1231 |
| ISSN: | 1538-0254 0739-1102 |
| DOI: | 10.1080/07391102.2015.1074113 |
| Popis: | The glucocorticoid receptor (GR), a transcription factor regulating gene expression in a ligand-dependent fashion, is known for flexibility in adapting various ligands with their structures ranging from steroid to non-steroid. However, in our previous study (Chen et al., 2011), GR shows a stringent discrimination against a set of steroid ligands with highly similar structures for triggering its nuclear migration. In order to resolve this puzzle, we employed molecular docking simulations to investigate the origin of this structural discrimination. By analyzing the docking orientations and the related ligand-GR interaction patterns, we found that the hydrophilicity mismatch between the docking ligand and the GR ligand-binding site is the main cause combined with the steric hindrance and structural rigidness of these steroid ligands. Furthermore we utilized this knowledge to rationalize how the structure-binding interaction of non-steroid ligands triggers GR nuclear migration with their structures available in Protein Data Bank. |
| Databáze: | OpenAIRE |
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