The SERMs are known to feature four distinctive modes of binding to ER. One of those features are strong hydrogen bonds between the ligand and ERα's Arg-394 and Glu-353 that line the „A-ring pocket“ and help the ligand to stay in ER's binding pocket. This is unlike 17β-estradiol which is hydrogen bonded to His-524 in the "D-ring pocket". Other distinctive bindings to the ligand-binding pocket are with a nearly planar “core” structure typically composed of a biaryl heterocycle, equivalent to the A-ring and B-ring of 17β-estradiol (see figure 14), to the corresponding binding site; a bulky side chain from the biaryl structure, analogous to the B-ring of 17β-estradiol and finally a second side group that is the C- and D-ring equivalent and usually aromatic, fills the remainder volume of the ligand-binding pocket.