title: Prediction of estrogen receptor β ligands potency and selectivity by docking and MM-GBSA scoring methods using three different scaffolds.
abstract: This study aimed to identify the docking and molecular mechanics-generalized born surface area (MM-GBSA) re-scoring parameters which can correlate the binding affinity and selectivity of the ligands towards oestrogen receptor β (ERβ). Three different series of ERβ ligands were used as dataset and the compounds were docked against ERβ (protein data bank (PDB) ID: 1QKM) using Glide and ArgusLab. Glide docking showed superior results when compared with ArgusLab. Docked poses were then rescored using Prime-MM-GBSA to calculate free energy binding. Correlations were made between observed activities of ERβ ligands with computationally predicted values from docking, binding energy parameters. ERβ ligands experimental binding affinity/selectivity did not correlate well with Glide and ArgusLab score. Whereas calculated Glide energy (coulomb-van der Waal interaction energy) correlated significantly with binding affinity of ERβ ligands (r(2) = 0.66). MM-GBSA re-scoring showed correlation of r(2) = 0.74 with selectivity of ERβ ligands. These results will aid the discovery of novel ERβ ligands with isoform selectivity.
authors: Department of Pharmacology, PSG College of Pharmacy, Coimbatore, India.
authors: B
authors: B
authors: Balaji
authors: M
authors: M
authors: Ramanathan
mesh_terms: D001665:Binding Sites; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000737:chemistry*; D019833:Genistein / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010091:Oximes / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*; D011485:Protein Binding; D020033:Protein Isoforms / Q000819:agonists / Q000737:chemistry; D012107:Research Design; D013816:Thermodynamics
chemical_list: D047629:Estrogen Receptor beta; D008024:Ligands; D010091:Oximes; D010636:Phenols; D020033:Protein Isoforms; D019833:Genistein