Document Detail


Development of a novel in silico docking simulation model for the fine HIV-1 cytotoxic T lymphocyte epitope mapping.
MedLine Citation:
PMID:  22848572     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: Class I HLA's polymorphism has hampered CTL epitope mapping with laborious experiments. Objectives are 1) to evaluate the novel in silico model in predicting previously reported epitopes in comparison with existing program, and 2) to apply the model to predict optimal epitopes with HLA using experimental results.
MATERIALS AND METHODS: We have developed a novel in silico epitope prediction method, based on HLA crystal structure and a peptide docking simulation model, calculating the peptide-HLA binding affinity at four amino acid residues in each terminal. It was applied to predict 52 HIV best-defined CTL epitopes from 15-mer overlapping peptides, and its predictive ability was compared with the HLA binding motif-based program of HLArestrictor. It was then used to predict HIV-1 Gag optimal epitopes from previous ELISpot results.
RESULTS: 43/52 (82.7%) epitopes were detected by the novel model, whereas 37 (71.2%) by HLArestrictor. We also found a significant reduction in epitope detection rates for longer epitopes in HLArestrictor (p = 0.027), but not in the novel model. Improved epitope prediction was also found by introducing both models, especially in specificity (p<0.001). Eight peptides were predicted as novel, immunodominant epitopes in both models.
DISCUSSION: This novel model can predict optimal CTL epitopes, which were not detected by an existing program. This model is potentially useful not only for narrowing down optimal epitopes, but predicting rare HLA alleles with less information. By introducing different principal models, epitope prediction will be more precise.
Authors:
Masahiko Mori; Kei Matsuki; Tomoyuki Maekawa; Mari Tanaka; Busarawan Sriwanthana; Masaru Yokoyama; Koya Ariyoshi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-27
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-07-31     Completed Date:  2013-04-09     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e41703     Citation Subset:  IM    
Affiliation:
Institute of Tropical Medicine, Nagasaki University, Nagasaki City, Nagasaki, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs
Amino Acid Sequence
Cohort Studies
Computational Biology*
Epitope Mapping / methods*
Epitopes, T-Lymphocyte / chemistry,  immunology*,  metabolism
Female
HIV Antigens / chemistry,  immunology
HIV-1 / chemistry*,  immunology*
HLA Antigens / chemistry,  immunology
Humans
Male
Molecular Docking Simulation*
T-Lymphocytes, Cytotoxic / immunology*
gag Gene Products, Human Immunodeficiency Virus / chemistry,  immunology
Chemical
Reg. No./Substance:
0/Epitopes, T-Lymphocyte; 0/HIV Antigens; 0/HLA Antigens; 0/gag Gene Products, Human Immunodeficiency Virus
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