Computational optimization of antibody humanness and stability by systematic energy-based ranking.

ABSTRACT: Conventional methods for humanizing animal-derived antibodies involve grafting their complementarity-determining regions onto homologous human framework regions. However, this process can substantially lower antibody stability and antigen-binding affinity, and requires iterative mutational fine-tuning to recover the original antibody properties. Here we report a computational method for the systematic grafting of animal complementarity-determining regions onto thousands of human frameworks. The method, which we named CUMAb (for computational human antibody design; available at http://CUMAb.weizmann.ac.il ), starts from an experimental or model antibody structure and uses Rosetta atomistic simulations to select designs by energy and structural integrity. CUMAb-designed humanized versions of

SUBMITTER: Tennenhouse A 

PROVIDER: S-EPMC10842793 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature