Optimizing antibody affinity and stability by the automated design of the variable light-heavy chain interfaces.

ABSTRACT: Antibodies developed for research and clinical applications may exhibit suboptimal stability, expressibility, or affinity. Existing optimization strategies focus on surface mutations, whereas natural affinity maturation also introduces mutations in the antibody core, simultaneously improving stability and affinity. To systematically map the mutational tolerance of an antibody variable fragment (Fv), we performed yeast display and applied deep mutational scanning to an anti-lysozyme antibody and found that many of the affinity-enhancing mutations clustered at the variable light-heavy chain interface, within the antibody core. Rosetta design combined enhancing mutations, yielding a variant with tenfold higher affinity and substantially improved stability. To make this approach broadly access

SUBMITTER: Warszawski S 

PROVIDER: S-EPMC6728052 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature