Structure guided homology model based design and engineering of mouse antibodies for humanization.

ABSTRACT: No universal strategy exists for humanizing mouse antibodies, and most approaches are based on primary sequence alignment and grafting. Although this strategy theoretically decreases the immunogenicity of mouse antibodies, it neither addresses conformational changes nor steric clashes that arise due to grafting of human germline frameworks to accommodate mouse CDR regions. To address these issues, we created and tested a structure-based biologic design approach using a de novo homology model to aid in the humanization of 17 unique mouse antibodies. Our approach included building a structure-based de novo homology model from the primary mouse antibody sequence, mutation of the mouse framework residues to the closest human germline sequence and energy minimization by simulated annealing on t

SUBMITTER: Kurella VB 

PROVIDER: S-EPMC4070046 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature