Computer-aided antibody design

Recent clinical trials using antibodies with low toxicity and high efficiency have raised expectations for the development of next-generation protein therapeutics. However, the process of obtaining therapeutic antibodies remains time consuming and empirical. This review summarizes recent progresses...

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Bibliographic Details
Published in:Protein engineering, design and selection design and selection, 2012-10, Vol.25 (10), p.507-522
Main Authors: Kuroda, Daisuke, Shirai, Hiroki, Jacobson, Matthew P., Nakamura, Haruki
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antibodies - chemistry
Antibodies - genetics
Antibodies - immunology
Antibody Affinity
Binding Sites, Antibody
Clinical trials
Computer applications
Computer-Aided Design
Crystal structure
Drug development
Energy
Homology
Humans
Immunoglobulin Subunits - chemistry
Immunoglobulin Subunits - genetics
Immunoglobulin Subunits - immunology
Immunoglobulin Variable Region - chemistry
Immunoglobulin Variable Region - genetics
Immunoglobulin Variable Region - immunology
Models, Molecular
Physicochemical properties
Protein Conformation
Review
Reviews
Toxicity
Vaccines
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Summary:Recent clinical trials using antibodies with low toxicity and high efficiency have raised expectations for the development of next-generation protein therapeutics. However, the process of obtaining therapeutic antibodies remains time consuming and empirical. This review summarizes recent progresses in the field of computer-aided antibody development mainly focusing on antibody modeling, which is divided essentially into two parts: (i) modeling the antigen-binding site, also called the complementarity determining regions (CDRs), and (ii) predicting the relative orientations of the variable heavy (VH) and light (VL) chains. Among the six CDR loops, the greatest challenge is predicting the conformation of CDR-H3, which is the most important in antigen recognition. Further computational methods could be used in drug development based on crystal structures or homology models, including antibody–antigen dockings and energy calculations with approximate potential functions. These methods should guide experimental studies to improve the affinities and physicochemical properties of antibodies. Finally, several successful examples of in silico structure-based antibody designs are reviewed. We also briefly review structure-based antigen or immunogen design, with application to rational vaccine development.
ISSN:1741-0126
1741-0134
DOI:10.1093/protein/gzs024