title: Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β.
abstract: Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q²) was 0.571 and non-cross-validation correlation coefficient (r²) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046, PR China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Wang
authors.forename: Xinzhou
authors.initials: X
authors.lastname: Wang
authors.forename: Hongling
authors.initials: H
authors.lastname: Liu
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
mesh_terms: D052244:Endocrine Disruptors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D055768:Halogenated Diphenyl Ethers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D021281:Quantitative Structure-Activity Relationship; D011988:Receptors, Thyroid Hormone / Q000737:chemistry* / Q000378:metabolism; D013963:Thyroid Hormones / Q000737:chemistry* / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D055768:Halogenated Diphenyl Ethers; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones