In Silico Methods in Antibody Design

Jun Zhao; Ruth Nussinov; Wen-Jin Wu; Buyong Ma

doi:10.3390/antib7030022

In Silico Methods in Antibody Design

Antibodies (Basel). 2018 Jun 29;7(3):22. doi: 10.3390/antib7030022.

Authors

Jun Zhao^{1

2

3}, Ruth Nussinov^{4

5}, Wen-Jin Wu⁶, Buyong Ma⁷

Affiliations

¹ Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. jun.zhao@nih.gov.
² Interagency Oncology Task Force (IOTF) Fellowship: Oncology Product Research/Review Fellow, National Cancer Institute, Bethesda, MD 20892, USA. jun.zhao@nih.gov.
³ Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA. jun.zhao@nih.gov.
⁴ Basic Science Program, Leidos Biomedical Research, Inc. Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA. nussinor@mail.nih.gov.
⁵ Sackler Inst. of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. nussinor@mail.nih.gov.
⁶ Division of Biotechnology Review and Research I, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Wen.Wu@fda.hhs.gov.
⁷ Basic Science Program, Leidos Biomedical Research, Inc. Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA. buyong.ma@nih.gov.

Abstract

Antibody therapies with high efficiency and low toxicity are becoming one of the major approaches in antibody therapeutics. Based on high-throughput sequencing and increasing experimental structures of antibodies/antibody-antigen complexes, computational approaches can predict antibody/antigen structures, engineering the function of antibodies and design antibody-antigen complexes with improved properties. This review summarizes recent progress in the field of in silico design of antibodies, including antibody structure modeling, antibody-antigen complex prediction, antibody stability evaluation, and allosteric effects in antibodies and functions. We listed the cases in which these methods have helped experimental studies to improve the affinities and physicochemical properties of antibodies. We emphasized how the molecular dynamics unveiled the allosteric effects during antibody-antigen recognition and antibody-effector recognition.

Keywords: affinity maturation; allosteric effect; antibody design; antibody stability; antibody-antigen recognition; epitope prediction; immunogenicity; vaccine design.

Publication types

Review