Identification of viable TCDD access pathways to human AhR PAS-B ligand binding domain

Unintentionally released in the environment as by-products of industrial activities, dioxins, exemplified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), represent a primary concern for human health. Exposure to these chemicals is known produce broad spectrum adverse effects, including cancer. The main mechanism action TCDD humans involves binding Aryl hydrocarbon Receptor (AhR). Although qualitatively established, capture AhR remains poorly characterized at molecular level. Starting from recently developed structural model PAS-B domain, this work we attempt identification viable access pathways ligand domain means dynamics. Based on result metadynamics simulations, identify two regions that may potentially serve paths TCDD. For each path, characterize residues closely interacting with TCDD, thereby suggesting possible capture. Our results are reviewed and discussed light available information about Human structure functions.