Antibody humanization by molecular dynamics simulations-in-silico guided selection of critical backmutations.

ABSTRACT: Monoclonal antibodies represent the fastest growing class of biotherapeutic proteins. However, as they are often initially derived from rodent organisms, there is a severe risk of immunogenic reactions, hampering their applicability. The humanization of these antibodies remains a challenging task in the context of rational drug design. "Superhumanization" describes the direct transfer of the complementarity determining regions to a human germline framework, but this humanization approach often results in loss of binding affinity. In this study, we present a new approach for predicting promising backmutation sites using molecular dynamics simulations of the model antibody Ab2/3H6. The simulation method was developed in close conjunction with novel specificity experiments. Binding properties

SUBMITTER: Margreitter C 

PROVIDER: S-EPMC4948679 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature