Computational Molecular Modeling Studies of the Interactions of Estrogens with Their Receptors and Intracellular Estrogen Binding Protein PDIp

Abstract

The endogenous estrogens are vitally-important female sex hormones with diverse biological functions. Disruption of their actions contributes to the pathogenesis of a number of disease states in humans, such as endocrine disruption, infertility, and development of cancers. My dissertation research sought to explore the potential usefulness of computational molecular modeling tools in studying the interactions of various estrogen derivatives (e.g., endogenous estrogen metabolites, non-aromatic steroids, and synthetic antiestrogens) with human ERs as well as a recently-identified intracellular estrogen-binding protein. The results of my dissertation projects offer important insights into the three-dimensional structural characteristics of the binding interactions of various estrogen analogs with the human ERs and PDIp. These studies provide a platform for the future development of an automated docking-based computational approach that can screen numerous environmental compounds for their potential ability to bind to human ERs as well as other estrogen binding proteins in the body.