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Updated: Aug 8, 2026

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Role of hydrophobic effects and polar groups in steroid-mineralocorticoid receptor interactions
Abstract:
To test whether hydrophobic interactions are the main driving forces in the association of steroids with mineralocorticoid receptors, the binding free energy calculated (delta Gc) using the surface area of the steroids accessible to water was compared with the observed free energy (delta GM) obtained from the Kd at the equilibrium estimated in the rat cytosol. The results are consistent with a binding process involving principally hydrophobic effects implying association of both faces of the steroid with the receptor. The discrepancies between calculated and observed values probably depend upon the mechanism of hydrogen bonding of the polar groups of the steroids to those on the receptor. Hydrogen bonds in an aqueous environment are likely between polar groups of the receptor and the 21-OH, 18-OH and 11-18 hemiacetal oxygen of the steroids. Strong hydrogen bonding in a hydrophobic environment from the 3-CO and 20-CO groups is a possibility (the latter with a dihedral angle C16-C17-C20-O20 of approximately equal to 7 degrees). Such a strong hydrogen bond from the 9 alpha-fluorine atom could account for the observed high affinity receptor binding of 9 alpha-fluorocortisol and 9 alpha-fluoroprednisolone. The loss of affinity in 11-deoxycortisol and cortisol may be explained by modification of the C17 side chain and repulsion forces from the 11 beta-OH.
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