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论文类型：期刊论文

发表时间：2017-09-01

发表刊物：CHEMOSPHERE

收录刊物：SCIE、EI、PubMed

卷号：182

页面范围：574-583

ISSN号：0045-6535

关键字：Ionizable halogenated alphatic compounds; Poly- and perfluorinated chemicals; Human transthyretin; In silico models; Ionization

摘要：Chemical forms-dependent binding interactions between phenolic compounds and human transthyretin (hTTR) have been elaborated previously. However, it is not known whether the binding interactions between ionizable halogenated alphatic compounds and hi fit also have the same manner. In this study, poly-/perfluorinated chemicals (PFCs) were selected as model compounds and molecular dynamic simulation was performed to investigate the binding mechanisms between PFCs and hTTR. Results show the binding interactions between the halogenated aliphatic compounds and hTTR are related to the chemical forms. The ionized groups of PFCs can form electrostatic interactions with the -NH3+ groups of Lys 15 residues in hTTR and form hydrogen bonds with the residues of hTTR. By analyzing the molecular orbital energies of PFCs, we also found that the anionic groups (nucleophile) in PFCs could form electron donor acceptor interactions with the -NH3+ groups (electrophile) in Lys 15. The aforementioned orientational interactions make the ionized groups of the PFCs point toward the entry port of the binding site. The roles of fluorine atoms in the binding interactions were also explored. The fluorine atoms can influence the binding interactions via inductive effects. Appropriate molecular descriptors were selected to characterize these interactions, and two quantitative structure-activity relationship models were developed. (C) 2017 Elsevier Ltd. All rights reserved.