Antibodies: Computer-Aided Prediction of Structure and Design of Function

Abstract

ABSTRACT With the advent of high-throughput sequencing, and the increased availability of experimental structures of antibodies and antibody-antigen complexes, comes the improvement of computational approaches to predict the structure and design the function of antibodies and antibody-antigen complexes. While antibodies pose formidable challenges for protein structure prediction and design due to their large size and highly flexible loops in the complementarity-determining regions, they also offer exciting opportunities: the central importance of antibodies for human health results in a wealth of structural and sequence information that—as a knowledge base—can drive the modeling algorithms by limiting the conformational and sequence search space to likely regions of success. Further, efficient experimental platforms exist to test predicted antibody structure or designed antibody function, thereby leading to an iterative feedback loop between computation and experiment. We briefly review the history of computer-aided prediction of structure and design of function in the antibody field before we focus on recent methodological developments and the most exciting application examples.