title: The interaction between organic phosphate ester and p53: an integrated experimental and in silico approach.
abstract: Concerns have been raised in regards to the environmental impact of the more used organophosphate flame retardants (OPFRs). In this study, to better understand the relationship between molecular structural features of OPFRs and binding affinity for the tumor suppressor p53, an integrated experimental and in silico approach was used. From docking analysis, hydrogen bonding and hydrophobic interactions were found to be the dominant interactions, which implied the binding affinities of the compounds. The binding constants of 5 OPFRs were determined by surface plasmon resonance technology (SPR). Based on the observed interactions, appropriate molecular structural parameters were adopted to develop a quantitative structure-activity relationship (QSAR) model. The developed QSAR model had good robustness, predictive ability and mechanism interpretability. The interactions between the OPFRs and p53 (Ebinding) and the partition ability of the OPFRs into the bio-phase are main factors governing the binding affinities.
authors.affiliation: Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), YICCAS, Yantai 264003, PR China; Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, YICCAS, Yantai 264003, PR China. Electronic address: fli@yic.ac.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, PR China.
authors.forename: Renmin
authors.initials: R
authors.lastname: Li
authors.affiliation: Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, Dalian 116024, PR China.
authors.forename: Xianhai
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), YICCAS, Yantai 264003, PR China; Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, YICCAS, Yantai 264003, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: You
authors.affiliation: Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), YICCAS, Yantai 264003, PR China; Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, YICCAS, Yantai 264003, PR China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Coastal Zone Environmental Processes and Ecological Remediation, Yantai Institute of Coastal Zone Research (YIC), Chinese Academy of Sciences (CAS), YICCAS, Yantai 264003, PR China; Shandong Provincial Key Laboratory of Coastal Zone Environmental Processes, YICCAS, Yantai 264003, PR China. Electronic address: hfwu@yic.ac.cn.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Wu
mesh_terms: D003198:Computer Simulation; D005411:Flame Retardants / Q000378:metabolism*; D016158:Genes, p53; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D016014:Linear Models; D062105:Molecular Docking Simulation; D010755:Organophosphates / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D005411:Flame Retardants; D010755:Organophosphates
keywords: Binding affinity; Docking; Multiple linear regression (MLR); Organophosphate flame retardants (OPFRs); Quantitative structure-activity relationship (QSAR); p53