Nuclear receptors (NR) are ligand-activated transcription factors that regulate the activation of a variety of important target genes, which are the most important drug targets in terms of potential therapeutic application. According to our results, secondary structure and polarizability play the major role in determining the drug-NRs interactions. The conservative motif of the NR is typically described as three stacked alpha-helical sheets. The helices that make up the ''front'' and ''back'' sheets are aligned parallel to one another. The helices in the middle sheet run across the two outer sheets and only occupy the space in the upper portion of the domain. The space in the lower part of the domain is relatively void of protein, and for most NRs, this creates an internal cavity for small-molecule ligands [110] . Hydrogen bonds with polarizability activity play a crucial role in protein-drug interactions (see, e.g., [11] ). Our approaches and the results thus obtained could be used to demonstrate how nuclear hormone receptors form a network of direct interactions. And this network increases in complexity to describe the interactions with target genes as well as small molecules known to bind a receptor, enzyme, or transporter.