Analysis of Affinity Energy Between Biphenyl Dioxygenase and Polychlorinated Biphenyls Using Molecular Docking

Molecular docking was used to calculate the affinity energy between biphenyl dioxygenases(BphA),including 1ULJ,1WQL,2YFJ,2YFL,2GBX,2XSH,2B4P,3GZX,and 3GZY(selected from the Protein Data Bank)and 209 polychlorinated biphenyl(PCB)congeners.The relationships between the calculated affinity energy and the persistent organic pollutant characteristics(migration,octanol-air partition coefficients,lgKOA;persistence,half-life,lgt1/2;toxicity,half-maximal inhibitory concentration,IgIC50;bioaccumulation,bioconcentration factor,lgBCF)of the PCBs were studied to mderstand the BphA mediated degradation of PCBs.The effect of substituent characteristics on the affinity energy was explored through full factorial experimental design.The affinities of nine kinds of BphA proteins on PCBs ranked as follows:2GBX>2YFJ>2YFL>3GZX>2XSH>3GZY>2E4P>1 WQL>1ULJ.The relationships between the calculated affinity energy and the molecular weight,lgKOA,lgBCF,and lgt1/2 of the PCBs were statistically signiflcant(p<0.01),whereas the relationship with the lgIC50 of PCBs was not statistically significant(p>0.05).PCBs were more difficult to degrade following an increase in the free energy of binding.Correlation analysis showed that the average affinity energy values of PCBs gradually increased as the number of chlorine atoms increased,regardless of the substituent position.The substituents at the ortho-positions interacted mainly through a second-order interaction,whereas those at the para-positions did not participate via a second-order interaction.

Prediction of Stability for Polychlorinated Biphenyls in Transformer Insulation Oil Through Three-dimensional Quantitative Structure-activity Relationship Pharmacophore Model and Full Factor Experimental Design

Based on the obtained data of half-lives（t1/2） for 31 polychlorinated biphenyl congeners（PCBs）, 3D quantitative structure-activity relationship（QSAR） pharmacophore was used to establish a 3D QSAR model to predict the t1/2 values of the remaining 178 PCBs, using the structural parameters as independent variables and lgt1/2 values as the dependent variable. Among this process, the whole data set（31 compounds） was divided into a training set（24 compounds） for model generation and a test set（7 compounds） for model validation. Then, the full factor experimental design was used to research the potential second-order interactional effect between different substituent positions, obtaining the final regulation scheme for PCB. At last, a 3D QSAR pharmacophore model was established to validate the reasonable regulation targeting typical PCB with respect to half-lives and thermostability. As a result, the cross-validation correlation coefficient（q2） obtained by the 3D QSAR model was 0.845（〉0.5） and the coefficient of determination（r2） obtained was 0.936（〉0.9）, indicating that the models were robust and predictive. CoMSIA analyses upon steric, electrostatic and hydrophobic fields were 0.7%, 85.9%, and 13.4%, respectively. The electrostatic field was determined to be a primary factor governing the tt/2. From CoMSIA contour maps, tl/2 increased when substi- tuents possessed electropositive groups at the 2＇-, 3-, Y-, 5- and 5＇- positions and electronegative groups at the 3-, 3＇-, 5-, 6- and 6＇- positions, which could increase the PCB stability in transformer insulation oil. Modification of two typical PCB congeners（PCB-77 and PCB-81） showed that the lgtl/2 for three selected modified compounds increased by 13%（average ratio） compared with that of each congener and the thermostability of them were higher, validating the reasonability of the regulatory scheme obtained from the 3D QSAR model. These results are expected to be beneficial in predicting tl/2 values of PCB homologues and derivatives and in providing a theoretical foundation for further elucidation of the stability of PCBs.