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Updated: May 14, 2026
08:09
Peptide Scanning-assisted Identification of a Monoclonal Antibody-recognized Linear B-cell Epitope
Published on: March 24, 2017
A structural bioinformatics approach for identifying proteins predisposed to bind linear epitopes on pre-selected
Eun Jung Choi1, Ron Jacak, Brian Kuhlman
1Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Protein Engineering, Design & Selection : PEDS
|January 24, 2013
Summary
We developed a method to find proteins that bind linear epitopes on disease targets. This approach identified binders for tuberculosis virulence factor and malaria apical membrane antigen, aiding therapeutic protein design.
Area of Science:
- Protein engineering
- Computational biology
- Immunology
Background:
- Identifying proteins that bind specific linear epitopes is crucial for developing targeted therapeutics.
- Current methods for epitope-based binder discovery are often inefficient and time-consuming.
Purpose of the Study:
- To develop and validate a computational protocol for identifying protein scaffolds that bind linear epitopes on target proteins.
- To demonstrate the utility of this protocol in discovering binders for medically relevant disease targets.
Main Methods:
- A database search for protein scaffolds with peptides similar to target epitopes.
- Utilizing scaffold-peptide crystal structures to model scaffold-epitope interactions.
- Employing sequence optimization and directed evolution to enhance binding affinity.
Main Results:
- Successfully identified protein binders for a tuberculosis virulence factor (TVF) and malaria apical membrane antigen (AMA).
- Achieved dissociation constants (Kds) of 37 μM for TVF and 50 nM for AMA.
- Developed a web server for scaffold searching with user-defined target sequences.
Conclusions:
- The developed protocol is effective for identifying protein scaffolds that bind linear epitopes.
- This computational approach accelerates the discovery of potential therapeutic agents targeting disease-related proteins.
- The web server provides a valuable resource for researchers in epitope-based drug design.
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