title: Investigation of the diastereomerism of dihydrobenzoxathiin SERMs for ER alpha by molecular modeling.
abstract: Molecular dynamics simulations were performed to investigate the distinct uterine activity of ten dihydrobenzoxathiin diastereomers against human estrogen receptor (ER) α. These diastereomers share similar binding mode to ER α ligand binding domain (LBD). Dihydrobenzoxathiin diastereomers with full antagonistic activity form more stable hydrogen bonds with Glu353 and His524 of ER α LBD than corresponding diastereomers. The molecular mechanics based generalized born surface area (MM-GBSA) analysis revealed that van der Waals interactions are predominant to the binding of dihydrobenzoxathiin diastereomers to ER α LBD. The per-residue free energy decomposition analysis revealed that the uterine activity difference is contributed mainly by electrostatic interactions. Our study provides mechanistic insights into the difference of uterine activity for dihydrobenzoxathiin diastereomers.
authors: Institute of Environmental Science, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Shulin
authors: S
authors: Zhuang
authors: Jing
authors: J
authors: Zhang
authors: Feng
authors: F
authors: Zhang
authors: Zhisheng
authors: Z
authors: Zhang
authors: Yuezhong
authors: Y
authors: Wen
authors: Weiping
authors: W
authors: Liu
mesh_terms: D001665:Binding Sites; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010075:Oxathiins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055672:Static Electricity; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D008024:Ligands; D010075:Oxathiins; D020845:Selective Estrogen Receptor Modulators; C500019:dihydrobenzoxathiin