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

Pernille Haste Andersen, Morten Nielsen and Ole Lund
Center for Biological Sequence Analysis, BioCentrum, Technical University of Denmark

Protein Science, 15:2558-2567, 2006


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 which 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 which 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.

The method is available at http://www.cbs.dtu.dk/services/DiscoTope

Supplementary material is available at http://www.cbs.dtu.dk/suppl/immunology/DiscoTope.php.


Morten Nielsen,