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 r2=0.74 with selectivity of ERβ ligands. These results will aid the discovery of novel ERβ ligands with isoform selectivity. © 2012 Informa UK, Ltd.