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. 2023:2552:361-374.
doi: 10.1007/978-1-0716-2609-2_20.

Optimizing Antibody-Antigen Binding Affinities with the ADAPT Platform

Traian Sulea  1 , Christophe Deprez  1 , Christopher R Corbeil  1 , Enrico O Purisima  2
Affiliations

Optimizing Antibody-Antigen Binding Affinities with the ADAPT Platform

Traian Sulea et al. Methods Mol Biol. 2023.

Abstract

The ADAPT (Assisted Design of Antibody and Protein Therapeutics) platform guides the selection of mutants that improve/modulate the affinity of antibodies and other biologics. Predicted affinities are based on a consensus z-score from three scoring functions. Computational predictions are interleaved with experimental validation, significantly enhancing the robustness of the design and selection of mutants. A key step is an initial exhaustive virtual single-mutant scan that identifies hot spots and the mutations predicted to improve affinity. A small number of proposed single mutants are then produced and assayed. Only the validated single mutants (i.e., having improved affinity) are used to design double and higher-order mutants in subsequent rounds of design, avoiding the combinatorial explosion that arises from random mutagenesis. Typically, with a total of about 30-50 designed single, double, and triple mutants, affinity improvements of 10- to 100-fold are obtained.

Keywords: Affinity maturation; Antibody design; Consensus scoring; Protein engineering; Virtual mutagenesis; Z-score.

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