Raloxifene, like 4-hydroxytamoxifen, binds to ERα with the hydroxyl group of its phenolic "A ring" (see figure 15) through hydrogen bonds with Arg-394 and Glu-353. In addition to these bonds, raloxifene forms a second hydrogen bond to ER through the side group of His-524 because of the presence of a second hydroxyl group in the “D ring” (see figure 15). This hydrogen bond is also unlike that between 17β-estradiol and His-524, as the imidazole ring of His-524 is rotated to counteract the difference of the oxygen position in raloxifene and in 17β-estradiol. Just like in 4-hydroxytamoxifen, the bulky side chain of raloxifene displaces helix 12.