(A) H11-12 loop of WT ERα LBD-E2 complex. (B) Superimposing the position of the phenolic oxygen of Y537 at 0.1-ns intervals for apo WT (red), WT-E2 (blue), and apo D538G mutant (green). (C) Mapping the mass density isosurface (0.75, i.e., 25th percentile) of the hydrophobic side chains in the linker region (V533, V534, P535, and L536). (D) Side-chain packing of the apo D538G structure compared to WT-E2. (E) Ramachandran analysis of residues 534–538 for the apo WT, WT-E2, and apo D538G MD simulations. (F) Time series of the solvent accessible surface area (SASA) for hydrophobic loop residues (533–536). LBD, ligand binding domain.