2019/07/25 by Ricardo Ugarte, Ugarte, Ricardo · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Computer Science · Medicine · #Alpha (finance) #BETA (programming language) #Binding energy #Binding site #Biochemistry #Biology #Biomolecules (q-bio.BM) #Biophysics #Chemistry #Cluster (spacecraft) #Computational Drug Discovery Methods #Computational chemistry #Computer science #Crystallography #Endocrinology #Estrogen #Estrogen and related hormone effects #Estrogen receptor #Estrogen receptor alpha #Estrogen receptor beta #FOS: Biological sciences #Free Radicals and Antioxidants #Genetics #Ligand (biochemistry) #Medicine #Molecular dynamics #Physics #Receptor #q-bio.BM
paper · pdf · doi:10.48550/arxiv.1907.10808
11 pages, 5 figures
arxiv created 2019/07/25 · openalex publication_date 2019/07/25 · arxiv updated 2019/07/26 · openalex created_date 2022/07/28 · openalex updated_date 2026/08/06
Estrogen receptors (ERs) are a group of proteins activated by 17β-estradiol. The endocrine-disrupting chemicals (EDCs) mimic estrogen action by bind directly to the ligand binding domain of ER. From this perspective, ER represent a good model for identifying and assessing the health risk of potential EDCs. This ability is best reflected by the ligand-ER binding energy. Multilayer fragment molecular orbital (MFMO) calculations were performed which allowed us to obtain the binding energy using a calculation scheme that considers the molecular interactions that occur on the following model systems: the bound and free receptor, 17β-estradiol and a water cluster. The bound and free receptor and 17β-estradiol were surrounded by a water shell containing the same number of molecules as the water cluster. The structures required for MFMO calculations were obtained from molecular dynamics simulations and cluster analysis. Attractive dispersion interactions were observed between 17β-estradiol and the binding site hydrophobic residues. In addition, strong electrostatic interactions were found between 17β-estradiol and the following charged/polarized residues: Glu 353, His 524 and Arg 394. The FMO2-RHF/STO-3G:MP2/6-31G(d) weighted binding energy was of -67.2 kcal/mol. We hope that the model developed in this study can be useful for identifying and assessing the health risk of potential EDCs.