title: Rational Selection of the 3D Structure of Biomacromolecules for Molecular Docking Studies on the Mechanism of Endocrine Disruptor Action.
abstract: Molecular modeling has become an essential tool in predicting and simulating endocrine disrupting effects of chemicals. A key prerequisite for successful application of molecular modeling lies in the correctness of 3D structure for biomacromolecules to be simulated. To date, there are several databases that can provide the experimentally-determined 3D structures. However, commonly, there are many challenges or disadvantageous factors, e.g., (a) lots of 3D structures for a given biomacromolecular target in the protein database; (b) the quality variability for those structures; (c) belonging to different species; (d) mutant amino acid residue in key positions, and so on. Once an inappropriate 3D structure of a target biomacromolecule was selected in molecular modeling, the accuracy and scientific nature of the modeling results could be inevitably affected. In this article, based on literature survey and an analysis of the 3D structure characterization of biomacromolecular targets belonging to the endocrine system in protein databases, six principles were proposed to guide the selection of the appropriate 3D structure of biomacromolecules. The principles include considering the species diversity, the mechanism of action, whether there are mutant amino acid residues, whether the number of protein chains is correct, the degree of structural similarity between the ligand in 3D structure and the target compounds, and other factors, e.g., the experimental pH conditions of the structure determined process and resolution.
authors.affiliation: Nanjing Institute of Environmental Science , Ministry of Environmental Protection, Nanjing 210042, China.
authors.forename: Xianhai
authors.initials: X
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology , Nanjing 210094, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Nanjing Institute of Environmental Science , Ministry of Environmental Protection, Nanjing 210042, China.
authors.forename: Jining
authors.initials: J
authors.lastname: Liu
authors.affiliation: Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences , Yantai 264003, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology , Dalian 116024, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Li
authors.affiliation: Nanjing Institute of Environmental Science , Ministry of Environmental Protection, Nanjing 210042, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Shi
authors.affiliation: Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology , Dalian 116024, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D052244:Endocrine Disruptors / Q000737:chemistry* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D016415:Sequence Alignment
chemical_list: C506487:ESR1 protein, human; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha