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Antibody Modeling: Implications for Engineering and Design

2000; Elsevier BV; Volume: 20; Issue: 3 Linguagem: Inglês

10.1006/meth.1999.0921

1095-9130

Veronica Morea, Arthur M. Lesk, Anna Tramontano,

T-cell and B-cell Immunology

Our understanding of the rules relating sequence to structure in antibodies has led to the development of accurate knowledge-based procedures for antibody modeling. Information gained from the analysis of antibody structures has been successfully exploited to engineer antibody-like molecules endowed with prescribed properties, such as increased stability or different specificity, many of which have a broad spectrum of applications both in therapy and in research. Here we describe a knowledge-based procedure for the prediction of the antibody-variable domains, based on the canonical structures method for the antigen-binding site, and discuss its expected accuracy and limitations. The rational design of antibody-based molecules is illustrated using as an example one of the most widely employed modifications of antibody structures: the humanization of animal-derived antibodies to reduce their immunogenicity for serotherapy in humans.