Ligand-Based Virtual Screening, Molecular Docking, and Molecular Dynamic Simulations of New β-Estrogen Receptor Activators with Potential for Pharmacological Obesity Treatment

Obesity is a pandemic and a serious health problem in developed and undeveloped countries. Activation of estrogen receptor beta (ER beta) has been shown to promote weight loss without modifying caloric intake, making it an attractive target for developing new drugs against obesity. This work aimed to predict new small molecules as potential ER fi activators. A ligandbased virtual screening of the ZINC15, PubChem, and Molport databases by substructure and similarity was carried out using the three-dimensional organization of known ligands as a reference. A molecular docking screening of FDA-approved drugs was also conducted as a repositioning strategy. Finally, selected compounds were evaluated by molecular dynamic simulations. Compounds 1 (-24.27 +/- 0.34 kcal/mol), 2 (-23.33 +/- 0.3 kcal/mol), and 6 (-29.55 +/- 0.51 kcal/mol) showed the best stability on the active site in complex with ER beta with an RMSD < 3.3 angstrom. RMSF analysis showed that these compounds do not affect the fluctuation of the C alpha of ER beta nor the compactness according to the radius of gyration. Finally, an in silico evaluation of ADMET showed they are safe molecules. These results suggest that new ER beta ligands could be promising molecules for obesity control.

Automated summary

Obesity is a global health issue, and this study aimed to predict new small molecules as potential ER beta activators for obesity control. Ligand-based virtual screening and molecular docking were used to identify potential compounds. Molecular dynamic simulations and ADMET evaluation showed that the selected compounds had good stability, safety, and potential for obesity control.