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Computational redesign of human respiratory syncytial virus epitope as therapeutic peptide vaccines against pediatric pneumonia
Shi X.2; Zheng J.1; Yan T.2
2018-04-01
Source PublicationJournal of Molecular Modeling
ISSN09485023 16102940
Volume24Issue:4
AbstractHuman respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. Here, the RSV fusion (F) glycoprotein epitope FFL was redesigned based on its complex crystal structure with motavizumab, an mAb drug in development for the prevention of RSV infections, aiming to obtain therapeutic peptide vaccines with high affinity to induce RSV-specific neutralizing antibodies. Computational modeling and analysis found that only a small region covering the helix-turn-helix (HTH) motif of FFL can directly interact with motavizumab and confer stability and specificity to the complex system, while the rest of the epitope primarily serves as a structural scaffold that stabilizes the HTH conformation of motavizumab-binding site. Molecular dynamics simulations revealed a large flexibility and intrinsic disorder for the isolated linear HTH peptide, which would incur a considerable entropy penalty upon binding to motavizumab. In this respect, the FFL epitope was redesigned by truncation, mutation, and cyclization to derive a number of small cyclic peptide immunogens. We also employed in vitro fluorescence-based assays to demonstrate that the linear epitope peptide has no observable affinity to motavizumab, whereas redesigned versions of the peptide can bind with a moderate or high potency. [Figure not available: see fulltext.].
KeywordFusion glycoprotein epitope Pediatric pneumonia Rational peptide vaccine design Respiratory syncytial virus
DOI10.1007/s00894-018-3613-z
URLView the original
Language英語
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Shanghai Minhang District Central Hospital
2.XuZhou Medical University
Recommended Citation
GB/T 7714
Shi X.,Zheng J.,Yan T.. Computational redesign of human respiratory syncytial virus epitope as therapeutic peptide vaccines against pediatric pneumonia[J]. Journal of Molecular Modeling,2018,24(4).
APA Shi X.,Zheng J.,&Yan T..(2018).Computational redesign of human respiratory syncytial virus epitope as therapeutic peptide vaccines against pediatric pneumonia.Journal of Molecular Modeling,24(4).
MLA Shi X.,et al."Computational redesign of human respiratory syncytial virus epitope as therapeutic peptide vaccines against pediatric pneumonia".Journal of Molecular Modeling 24.4(2018).
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