A theoretical investigation of the conformation changing of dioxins in thebinding site of dioxin receptor model; role of absolute hardness-electronegativity activity diagrams for biological activity

To investigate the interaction with the binding site of dioxin receptor of dioxins, we analyzed the structure and energy for the 2,3,7,8-TCDD- and 1,4 ,6,9-TCDD-amino acid residue complex, respectively, by calculation using th e semiempirical AM1 method. It was found that the glutamine residue plays a n important role in the formation of an energetically stable complex with d ioxin. Particularly, toxic 2,3,7,8-TCDD is easily bound with the dioxin rec eptor, and the complex is nearly planar and most energerically stable. Howe ver, the structure of 1,4,6,9-TCDD is folded, and the value of absolute har dness increases. This means that 2,3,7,8-TCDD binds with the dioxin recepto r more strongly than 1,4,6,9-TCDD. As a result, we propose a dioxin binding site model, -Asn-Phe-Gln(-CONH2 ... 2,3,7,8-TCDD)-Gly-Arg-. We conclude th at the eta-chi activity diagram can apply to the model of the ligand bindin g site in the dioxin receptor. (C) 1999 Elsevier Science B.V. All rights re served.