title: Study on the agonists for the human Toll-like receptor-8 by molecular modeling.
abstract: Toll-like receptor-8 agonists could be promising candidates for vaccine adjuvants, especially for neonatal vaccines. In this study, we established reliable models and explored valuable information which could explain the known experimental facts at the molecular level. Firstly, we divided the whole dataset into four splits and obtained many dependable models based on the simplified molecular input line entry system (SMILES). Secondly, the whole dataset was divided into three splits and other reliable comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were established. Thirdly, we validated the prediction ability of these models using various validation methods for the test set. Lastly, for a better understanding of the binding modes between agonists and Toll-like receptor-8, molecular docking was applied to reveal the structural factors that impact the activity of agonists towards Toll-like receptor-8. Furthermore, molecular dynamics simulation was employed to further validate the docking results. The results obtained from molecular modeling support each other, which not only provides models to predict the activities of agonists but also leads to a better understanding of the essential features that should be considered when designing novel agonists with desired activities.
authors.affiliation: College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, Gansu, People's Republic of China. xyzhang@lzu.edu.cn.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Deng
authors.forename: Shuying
authors.initials: S
authors.lastname: Ma
authors.forename: Meihong
authors.initials: M
authors.lastname: Xie
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.forename: Peizhen
authors.initials: P
authors.lastname: Li
authors.forename: Honglin
authors.initials: H
authors.lastname: Zhai
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D021281:Quantitative Structure-Activity Relationship; D051200:Toll-Like Receptor 8 / Q000819:agonists* / Q000737:chemistry*
chemical_list: C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8