ABSTRACT
Endocrine disrupting chemicals (EDCs) are either natural or synthetic chemicals that directly or indirectly enhance (agonist effect) or inhibit (antagonist effect) the action of hormones that bind to specic nuclear receptors (NRs). NRs are important transcriptional regulators involved in diverse physiological functions such as control of homeostasis, cell differentiation, and embryonic development. In the absence of NR X-ray crystal structures, computer-aided molecular modeling becomes an alternative tool to provide in silico predictions of three-dimensional (3D) models of such receptors. Moreover, advances in comparative (homology) modeling algorithms, in addition to the increase in experimental protein structure information, allow the generation of homology models for a signicant portion of known genomic protein sequences. The aim of this chapter is to provide an overview of the 3D homology models of the NR superfamily. Such models are of considerable value, allowing for the understanding of EDC-receptor interactions and the generation of Structure-Activity Relationship (SAR) or 3D Quantitative Structure-Activity Relationship (QSAR) models. The strengths and weaknesses of the homology models applied to the EDCs are also analyzed.
