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.
CITATION STYLE
Sulea, T., Deprez, C., Corbeil, C. R., & Purisima, E. O. (2023). Optimizing Antibody–Antigen Binding Affinities with the ADAPT Platform. In Methods in Molecular Biology (Vol. 2552, pp. 361–374). Humana Press Inc. https://doi.org/10.1007/978-1-0716-2609-2_20
Mendeley helps you to discover research relevant for your work.