Molecular docking of dihydroxy polychlorinated biphenyls, which are atmospheric degradation products of dioxin-like polychlorinated biphenyls(PCBs), with dihydroxybiphenyl dioxygenase(Bphc, PDB ID: 1KW6) was studied, and the comparative molecular similarity indices analysis(CoMSIA) and the hologram quantitative structure-activity relationship(HQSAR) model were constructed, in which the molecular structure parameters as independent variables and total score(Kd, representing the docking activity) as the dependent variable, meanwhile, molecular modification of dihydroxy polychlorinated biphenyls was carried out. The results showed that Bphc enzymes can degrade all kinds of dihydroxy polychlorinated biphenyls in different degrees; the amino acid residues(His145, Val147, Ile174, His194, His208, His209, His240, Asn242, Tyr249, Thr280) affect the docking activity of Bphc enzyme, and also, more the hydrogen bond formed by the docking of dihydroxy polychlorinated biphenyls with amino acid residues, the higher the docking activity. A method for accurate determination of molecular substitution activity of dihydroxy polychlorinated biphenyls coupled with CoMSIA and HQSAR model was established. Based on the above, the 5,6-2OH-CB60 was as the target molecule, and eight novel molecules with improved scoring function were designed, whose docking activity increased 65%—185%, toxicity(IC50) decreased 10%—83%, bioaccumulation(BCF) decreased 4%—27%, migration(KOA) and half-life(t1/2) remained unchanged. The synthesis of the reaction pathways of novel molecules could confirm that the dihydroxy polychlorinated biphenyls 5,6-2OH-CB60 can react with active radicals and active molecules to form novel 5,6-2OH-CB60 molecules, which means the dioxin-like polychlorinated biphenyls can be degraded by atmospheric oxidation to produce a new type of two dihydroxy polychlorinated biphenyl whose enzyme degradation is remarkably improved, so as to further control the environmental behavior of dioxin-like PCBs.
