Biological enrichment prediction of polychlorinated biphenyls and novel molecular design based on 3D-QSAR/HQSAR associated with molecule docking

Jiawen Yang; Wenwen Gu; Yu Li

doi:10.1042/BSR20180409

Biological enrichment prediction of polychlorinated biphenyls and novel molecular design based on 3D-QSAR/HQSAR associated with molecule docking

Biosci Rep. 2019 May 17;39(5):BSR20180409. doi: 10.1042/BSR20180409. Print 2019 May 31.

Authors

Jiawen Yang^{1

2}, Wenwen Gu^{1

2}, Yu Li^{3

2}

Affiliations

¹ College of Environmental Science and Engineering, North China Electric Power University, Beijing, China.
² Moe Key Laboratory of Resources and Environmental Systems Optimization, North China Electric Power University, Beijing, China.
³ College of Environmental Science and Engineering, North China Electric Power University, Beijing, China liyuxx8@hotmail.com.

Abstract

Based on the experimental data of octanol-water partition coefficients (K_ow, represents bioaccumulation) for 13 polychlorinated biphenyl (PCB) congeners, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to establish 3D-QSAR models, combined with the hologram quantitative structure-activity relationship (HQSAR), the substitution sites (mono-substituted and bis-substituted) and substituent groups (electron-withdrawing hydrophobic groups) that significantly affect the octanol-water partition coefficients values of PCBs were identified, a total of 63 monosubstituted and bis-substituted were identified. Compared with using 3D-QSAR model alone, the coupling of 3D-QSAR and HQSAR models greatly increased the number of newly designed bis-substituted molecules, and the logK_ow reduction in newly designed bis-substituted molecules was larger than that of monosubstituted molecules. This was established to predict the K_ow values of 196 additional PCBs and carry out a modification of target molecular PCB-207 to lower its K_ow (biological enrichment) significantly, simultaneously maintaining the flame retardancy and insulativity after calculation by using Gaussian09. Simultaneously, molecular docking could further screen out three more environmental friendly low biological enrichment newly designed PCB-207 molecules (5-methyl-PCB-207, 5-amino-PCB-207, and 4-amino-5-ethyl-PCB-207).

Keywords: 3D-QSAR; HQSAR; PCBs; biological enrichment; molecular docking; molecular modification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Electrons
Hydrophobic and Hydrophilic Interactions
Molecular Conformation
Molecular Docking Simulation
Polychlorinated Biphenyls / chemistry*
Quantitative Structure-Activity Relationship
Water / chemistry

Substances

Water
Polychlorinated Biphenyls