In this work, we investigate the mode of binding of several steroid hormones, namely aldosterone, deoxycorticosterone, and progesterone to the wild-type and S810L mutated mineralocorticoid (MR) receptor using the newly formulated density functional theory with an empirical dispersion term (DFT-D) molecular electronic structure method. It is found that the MR agonists, aldosterone and deoxycorticosterone, form tight hydrogen bonds with residues Thr945 and Asn770, which leads to the formation of hydrogen bond networks near the steroid D-ring, allowing for activation of this transcription factor. Progesterone, an MR antagonist, fails to form the necessary hydrogen bonds near the steroid D-ring. Progesterone is known to be an agonist of the mutated S810L MR receptor. Our studies indicate that this is possible because of a strong hydrogen bond between progesterone and Thr945 and a relatively strong hydrophobic interaction between progesterone and Asn770.