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Published on: March 24, 2017
Automated detection of conformational epitopes using phage display Peptide sequences
Surendra S Negi1, Werner Braun
1Sealy Center for Structural Biology and Molecular Biophysics, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston TX, 77555-0857, USA.
Bioinformatics and Biology Insights
|February 9, 2010
Summary
EpiSearch is a new automated method that predicts conformational epitopes on antigens using phage display peptide data. It accurately identifies epitope locations, aiding vaccine design.
Area of Science:
- Immunology
- Structural Biology
- Bioinformatics
Background:
- Determining conformational epitopes of neutralizing antibodies is crucial for rational vaccine design.
- Phage display technology selects peptides (mimotopes) that bind monoclonal antibodies, offering insights into epitope characteristics.
- Interpreting these mimotopes for structural epitope characterization has been challenging, often relying on linear sequence analysis.
Purpose of the Study:
- To present EpiSearch, a fully automated method for predicting conformational epitope locations on antigen surfaces.
- To validate EpiSearch's performance using diverse experimental phage display data sets.
Main Methods:
- EpiSearch algorithm utilizes peptide sequences from phage display experiments as input.
- It ranks surface-exposed antigen patches based on residue similarity frequencies between peptides and patches.
- The method allows mapping of single or multiple peptides onto antigen structures and provides interactive web server visualization.
Main Results:
- EpiSearch successfully predicted conformational epitopes for six diverse experimental datasets, including HER-2/neu, FVIII, HIV gp120, HIV capsid protein, and SARS-CoV spike protein.
- In all tested cases, experimentally determined conformational epitopes were located within the highest-scoring patches identified by EpiSearch.
- The predicted epitope regions covered over 50% of the experimentally observed residues in most instances.
Conclusions:
- EpiSearch provides an effective and automated approach for predicting conformational epitope locations.
- The method aids in the structural characterization of epitopes derived from phage display mimotopes.
- This tool facilitates rational vaccine design by accurately pinpointing key antigenic regions.
