title: Determination and prediction of the binding interaction between organophosphate flame retardants and p53.
abstract: Organophosphate flame retardants (OPFRs) have caused widespread concern because of the harm to the environment. In this study, to better explain the mechanism for the binding of OPFRs with the tumor suppressor gene p53, an integrated experimental and in silico approach was used. The binding constants of 10 OPFRs were measured by surface plasmon resonance technology (SPR). The effect of OPFRs on p53 gene and protein expression in ZF4 cells was determined by quantitative real-time PCR and Western blotting. Molecular docking and dynamics simulation were explored to find that the H-bonds and hydrophobic interactions were the dominant interaction between OPFRs and p53. On the basis of the observed interactions, proper molecular structural descriptors were used to build the quantitative structure-activity relationship (QSAR) model. The current QSAR model provided robustness, predictive ability, and mechanism interpretability. The applicability domain of the QSAR was discussed by the Williams plot. The results showed that H-bonds and electrostatic interaction governed the binding affinities between OPFRs and p53.
authors.affiliation: Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences(CAS) , Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, YICCAS, Yantai Shandong 264003, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Xianhai
authors.initials: X
authors.lastname: Yang
authors.forename: Xuehua
authors.initials: X
authors.lastname: Li
authors.forename: Renmin
authors.initials: R
authors.lastname: Li
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhao
authors.forename: Huifeng
authors.initials: H
authors.lastname: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D004785:Environmental Pollutants / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005411:Flame Retardants / Q000378:metabolism* / Q000633:toxicity; D006860:Hydrogen Bonding; D007700:Kinetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010755:Organophosphates / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D004785:Environmental Pollutants; D005411:Flame Retardants; D010755:Organophosphates; D016159:Tumor Suppressor Protein p53