ABSTRACT
Rational drug design in the 1990s is increasingly based on knowledge of 3D-structure of the active sites of proteins that enables the chemist to imagine ligands with the appropriate fit and reactivity to induce or block biological action. In the field of steroid hormones, such an approach is not yet feasible since no integral steroid hormone receptor (SHR) has been sufficiently purified to be crystallized. Steroid binding is the primary function of the SHR but, in order to be effective in inducing the biological end point, it has to set into motion or enhance some of the other functions. 3D modeling of the hormone-binding domain of the steroid hormone receptor together with localization of domain functions and of amino acids involved in steroid binding and analysis of binding and activity data for large numbers of diversely substituted steroids, are still far from converging into a single unified vision of the mechanisms of steroid action.
