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

Abstract

Based on the experimental data of octanol-water partition coefficients (Kow, 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 logKow reduction in newly designed bis-substituted molecules was larger than that of monosubstituted molecules. This was established to predict the Kow values of 196 additional PCBs and carry out a modification of target molecular PCB-207 to lower its Kow (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).

Structural investigation of Keap1–Nrf2 protein–protein interaction (PPI) inhibitors for treating myocarditis through molecular simulations

“…26 In the modeling study, we randomly divided the 43 compounds into a training set and a test set with a ratio of roughly 3 : 1, in which the training group included 33 molecules (indicated by the superscript symbol ''*'') and the test group contained 10 molecules. 27 Molecular construction and structural optimization of these compounds were executed utilizing the molecular manipulation tool SYBYL-X 2.0. Tripos force field and Powell's energy gradient method were adopted to minimize the energy of all small molecules.…”

Mitigating the Adverse Effects of Polychlorinated Biphenyl Derivatives on Estrogenic Activity via Molecular Modification Techniques

“…Bonefeld-Jorgensen et al [ 15 ] studied the anti-androgenic activity of 3 PCBs in Chinese hamster ovary cells through a luciferase reporter gene experiment and found that the anti-androgenic activity of PCB-153 and PCB-180 was significantly less than that of PCB-138. Although PCBs were prohibited from being produced and used worldwide in the 1970s and listed in the Stockholm Convention on Persistent Organic Pollutants [ 16 , 17 , 18 ], the risk of anti-oestrogenic activity, by a large number of PCBs remaining in the environment, still cannot be ignored. How to effectively regulate and avoid them so as to reduce the damage to human health and environmental pollution is a trending issue that needs to be addressed.…”