Prediction of residues in discontinuous B-cell epitopes using protein 3D structures

Protein Sci. 2006 Nov;15(11):2558-67. doi: 10.1110/ps.062405906. Epub 2006 Sep 25.


Discovery of discontinuous B-cell epitopes is a major challenge in vaccine design. Previous epitope prediction methods have mostly been based on protein sequences and are not very effective. Here, we present DiscoTope, a novel method for discontinuous epitope prediction that uses protein three-dimensional structural data. The method is based on amino acid statistics, spatial information, and surface accessibility in a compiled data set of discontinuous epitopes determined by X-ray crystallography of antibody/antigen protein complexes. DiscoTope is the first method to focus explicitly on discontinuous epitopes. We show that the new structure-based method has a better performance for predicting residues of discontinuous epitopes than methods based solely on sequence information, and that it can successfully predict epitope residues that have been identified by different techniques. DiscoTope detects 15.5% of residues located in discontinuous epitopes with a specificity of 95%. At this level of specificity, the conventional Parker hydrophilicity scale for predicting linear B-cell epitopes identifies only 11.0% of residues located in discontinuous epitopes. Predictions by the DiscoTope method can guide experimental epitope mapping in both rational vaccine design and development of diagnostic tools, and may lead to more efficient epitope identification.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen-Antibody Complex / chemistry
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / immunology
  • Epitope Mapping / methods*
  • Epitopes, B-Lymphocyte / chemistry*
  • Imaging, Three-Dimensional / methods*
  • Membrane Proteins / chemistry
  • Membrane Proteins / immunology
  • Models, Molecular
  • Odds Ratio
  • Plasmodium falciparum
  • Protein Structure, Secondary
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / immunology


  • Antigen-Antibody Complex
  • Antigens, Protozoan
  • Epitopes, B-Lymphocyte
  • Membrane Proteins
  • Protozoan Proteins
  • apical membrane antigen I, Plasmodium