Figure 1.

Overview of the structure-based antibody humanization method. (left) Humanness is evaluated by the human string content (HSC) score,⁷ which calculates aligned nonamer matches against human antibody germline sequences. (right) Structural stability is evaluated by rotameric energy, comprised of position-specific terms for rotamers at individual positions (side-chain internal energy plus backbone interaction) and pairs of positions (side-chain interactions). (center) Sets of mutations are chosen so as to make optimal trade-offs between the competing humanness and energy scores. Fab structures are colored bluer for higher HSC.