Computational identification of antigen-binding antibody fragments.

Anat Burkovitz, Olga Leiderman, Inbal Sela-Culang, Gerardo Byk, Yanay Ofran

The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.

Journal of immunology (Baltimore, Md. : 1950) 2013 Mar 1

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Determining which parts of the Ab are essential for Ag recognition and binding is crucial for understanding B cell-mediated immunity. Identification of fragments of Abs that maintain specificity to the Ag will also allow for the development of improved Ab-based therapy and diagnostics. In this article, we show that structural analysis of Ab-Ag complexes reveals which fragments of the Ab may bind the Ag on their own. In particular, it is possible to predict whether a given CDR is likely to bind the Ag as a peptide by analyzing the energetic contribution of each CDR to Ag binding and by assessing to what extent the interaction between that CDR and the Ag depends on other CDRs. To demonstrate this, we analyzed five Ab-Ag complexes and predicted for each of them which of the CDRs may bind the Ag on its own as a peptide. We then show that these predictions are in agreement with our experimental analysis and with previously published experimental results. These findings promote our understanding of the modular nature of Ab-Ag interactions and lay the foundation for the rational design of active CDR-derived peptides.

Citation

Anat Burkovitz, Olga Leiderman, Inbal Sela-Culang, Gerardo Byk, Yanay Ofran. Computational identification of antigen-binding antibody fragments. Journal of immunology (Baltimore, Md. : 1950). 2013 Mar 1;190(5):2327-34