title: Investigation on critical structural motifs of ligands for triggering glucocorticoid receptor nuclear migration through molecular docking simulations.
abstract: 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, 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.
authors.affiliation: a Department of Chemistry , National Chung Hsing University , Taichung , Taiwan.
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Liu
authors.affiliation: b Department of Chemistry , Sejong University , Seoul 143-747 , Korea.
authors.forename: Soonmin
authors.initials: S
authors.lastname: Jang
authors.affiliation: c Institute of Nuclear Energy Research , Lungtan, Taoyuan , Taiwan.
authors.forename: Shih-Min
authors.initials: SM
authors.lastname: Wang
authors.affiliation: d General Education Center, Wenzao Ursuline University of Languages , Kaohsiung , Taiwan.
authors.forename: Chiu-Hao
authors.initials: CH
authors.lastname: Chen
authors.affiliation: a Department of Chemistry , National Chung Hsing University , Taichung , Taiwan.
authors.forename: Feng-Yin
authors.initials: FY
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus; D005938:Glucocorticoids / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011965:Receptors, Glucocorticoid / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D008024:Ligands; D011965:Receptors, Glucocorticoid
keywords: glucocorticoid receptor; molecular docking simulation; nuclear migration; solvent-exposed hydrophobic groove