Molecular modeling has given important contributions to elucidation of the main stages in the AhR signal transduction pathway. Despite the lack of experimentally determined structures of the AhR functional domains, information derived from homologous systems has been exploited for modeling their structure and interactions. Homology models of the AhR PASB domain have provided information on the binding cavity and contributed to elucidate species-specific differences in ligand binding. Molecular Docking simulations of the ligand binding process have given insights into differences in binding of diverse agonists, antagonists, and selective AhR modulators, and their application to virtual screening of large databases of compounds have allowed identification of novel AhR ligands. Recently available structural information on protein–protein and protein-DNA complexes of other bHLH-PAS systems has opened the way for modeling the AhR:ARNT dimer structure and investigating the mechanisms of AhR transformation and DNA binding. Future research directions should include simulation of the protein dynamics to obtain a more reliable description of intermolecular interactions involved in signal transmission.

Bonati, L., Corrada, D., GIANI TAGLIABUE, S., Motta, S. (2017). Molecular modeling of the AhR structure and interactions can shed light on ligand-dependent activation and transformation mechanisms. CURRENT OPINION IN TOXICOLOGY, 1, 42-49 [10.1016/j.cotox.2017.01.011].

Molecular modeling of the AhR structure and interactions can shed light on ligand-dependent activation and transformation mechanisms

BONATI, LAURA
;
CORRADA, DARIO;GIANI TAGLIABUE, SARA;MOTTA, STEFANO
2017

Abstract

Molecular modeling has given important contributions to elucidation of the main stages in the AhR signal transduction pathway. Despite the lack of experimentally determined structures of the AhR functional domains, information derived from homologous systems has been exploited for modeling their structure and interactions. Homology models of the AhR PASB domain have provided information on the binding cavity and contributed to elucidate species-specific differences in ligand binding. Molecular Docking simulations of the ligand binding process have given insights into differences in binding of diverse agonists, antagonists, and selective AhR modulators, and their application to virtual screening of large databases of compounds have allowed identification of novel AhR ligands. Recently available structural information on protein–protein and protein-DNA complexes of other bHLH-PAS systems has opened the way for modeling the AhR:ARNT dimer structure and investigating the mechanisms of AhR transformation and DNA binding. Future research directions should include simulation of the protein dynamics to obtain a more reliable description of intermolecular interactions involved in signal transmission.
Articolo in rivista - Review Essay
Molecular modeling; Molecular docking; Molecular dynamics; Ligand-binding; Protein–protein interactions; Dimerization
English
42
49
8
Bonati, L., Corrada, D., GIANI TAGLIABUE, S., Motta, S. (2017). Molecular modeling of the AhR structure and interactions can shed light on ligand-dependent activation and transformation mechanisms. CURRENT OPINION IN TOXICOLOGY, 1, 42-49 [10.1016/j.cotox.2017.01.011].
Bonati, L; Corrada, D; GIANI TAGLIABUE, S; Motta, S
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/147861
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