Improving B-cell epitope prediction and its application to global antibody-antigen docking

• Published in: Bioinformatics (Oxford, England) England), 2014-08, Vol.30 (16), p.2288-2294
• Main Authors: Krawczyk, Konrad, Liu, Xiaofeng, Baker, Terry, Shi, Jiye, Deane, Charlotte M
• Format: Article
• Language: English
• Subjects: Algorithms; Antigen-Antibody Complex - chemistry; Epitopes, B-Lymphocyte - chemistry; Humans; Molecular Docking Simulation - methods; Original Papers; Software
• ISSN: 1367-4803; 1367-4811
• DOI: 10.1093/bioinformatics/btu190

Antibodies are currently the most important class of biopharmaceuticals. Development of such antibody-based drugs depends on costly and time-consuming screening campaigns. Computational techniques such as antibody-antigen docking hold the potential to facilitate the screening process by rapidly providing a list of initial poses that approximate the native complex. We have developed a new method to identify the epitope region on the antigen, given the structures of the antibody and the antigen-EpiPred. The method combines conformational matching of the antibody-antigen structures and a specific antibody-antigen score. We have tested the method on both a large non-redundant set of antibody-antigen complexes and on homology models of the antibodies and/or the unbound antigen structure. On a non-redundant test set, our epitope prediction method achieves 44% recall at 14% precision against 23% recall at 14% precision for a background random distribution. We use our epitope predictions to rescore the global docking results of two rigid-body docking algorithms: ZDOCK and ClusPro. In both cases including our epitope, prediction increases the number of near-native poses found among the top decoys. Our software is available from http://www.stats.ox.ac.uk/research/proteins/resources.