Estrogen receptors (ERs)are nuclear transcription factor receptorsthat play important roles in gene expression and cell cycle regulation. Because of their ligand-activated signaling implication in carcinogenesis,ERs are extensively researched as protein targets for anti-cancer drug discovery active in certain types of tumors. However, a major drawback is the emergence of wild type tumors withoverexpressed mutant variants of ER, which become resistant to estrogen inhibitor drugs. Herein we studied the binding mode and affinity of the semisynthetic estrogen agonist, 17-b-estradiol (E2) in normal and mutant variants of ERs, by means of molecular docking. Our results showed a small decrease in binding affinity, recorded in mutant variants of ERa and a change in the binding interactions formed when the compound wasdocked in an agonist-bound conformation of the ERa . Nevertheless we concluded that even if the binding affinity showed a small decrease in the case of mutant type receptors,E2 potency towards ER�won�t register a downward trend.