Antibody design is a challenging task that could be improved by understanding antibody affinity maturation, a critical process by which antibodies gain affinity and specificity for antigen targets by introducing mutations. However, how these mutations affect antibody dynamics, specifically whether antibodies become more rigid as they mature, is still a highly contested topic. Using adaptive sampling molecular dynamics simulations, we demonstrate that the dynamics that accompany affinity maturation are highly dependent on the antigen binding site. We find that the antibody complementarity determining regions, CDR loops that contact the antigen directly do gain rigidity with maturation, but CDR loops that contact glycans gain flexibility. We show that using the principles from this study to manipulate dynamics may help improve binding affinity to antigens. These findings can be applied for precise engineering of antibodies in creating new monoclonal therapeutics for various diseases, optimizing current therapeutics to be more effective, and designing better antigens for vaccines.
Solieva et al. (Sun,) studied this question.