title: Antibody modeling: implications for engineering and design.
abstract: 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.
authors.affiliation: IRBM "P. Angeletti,", Via Pontina Km. 30.600, Pomezia, 00040, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Morea
authors.forename: A M
authors.initials: AM
authors.lastname: Lesk
authors.forename: A
authors.initials: A
authors.lastname: Tramontano
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D001665:Binding Sites; D008958:Models, Molecular; D011487:Protein Conformation; D015202:Protein Engineering
chemical_list: D000906:Antibodies