title: Effects of the hydroxyl group on phenyl based ligand/ERRγ protein binding.
abstract: Bisphenol-A (4,4'-dihydroxy-2,2-diphenylpropane, BPA, or BPA-A) and its derivatives, when exposed to humans, may affect functions of multiple organs by specific binding to the human estrogen-related receptor γ (ERRγ). We carried out atomistic molecular dynamics (MD) simulations of three ligand compounds including BPA-A, 4-α-cumylphenol (BPA-C), and 2,2-diphenylpropane (BPA-D) binding to the ligand binding domain (LBD) of a human ERRγ to study the structures and energies associated with the binding. We used the implicit Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method to estimate the free energies of binding for the phenyl based compound/ERRγ systems. The addition of hydroxyl groups to the aromatic ring had only a minor effect on binding structures and a significant effect on ligand/protein binding energy in an aqueous solution. Free binding energies of BPA-D to the ERRγ were found to be considerably less than those of BPA-A and BPA-C to the ERRγ. These results are well correlated with those from experiments where no binding affinities were determined in the BPA-D/ERRγ complex. No conformational change was observed for the helix 12 (H-12) of ERRγ upon binding of these compounds preserving an active transcriptional conformation state.
authors.affiliation: Department of Chemistry, Wayne State University , Detroit, Michigan 48202, United States.
authors.forename: Oleg N
authors.initials: ON
authors.lastname: Starovoytov
authors.forename: Yalin
authors.initials: Y
authors.lastname: Liu
authors.forename: Liuxi
authors.initials: L
authors.lastname: Tan
authors.forename: Shizhong
authors.initials: S
authors.lastname: Yang
mesh_terms: D001559:Benzhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D010636:Phenols / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism*; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D008024:Ligands; D010636:Phenols; D011960:Receptors, Estrogen; D012997:Solvents; C490917:ESRRG protein, human; C516284:4-cumylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds
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