Table_1_Local and Global Rigidification Upon Antibody Affinity Maturation.DOCX

During the affinity maturation process the immune system produces antibodies with higher specificity and activity through various rounds of somatic hypermutations in response to an antigen. Elucidating the affinity maturation process is fundamental in understanding immunity and in the development of biotherapeutics. Therefore, we analyzed 10 pairs of antibody fragments differing in their specificity and in distinct stages of affinity maturation using metadynamics in combination with molecular dynamics (MD) simulations. We investigated differences in flexibility of the CDR-H3 loop and global changes in plasticity upon affinity maturation. Among all antibody pairs we observed a substantial rigidification in flexibility and plasticity reflected in a substantial decrease of conformational diversity. To visualize and characterize these findings we used Markov-states models to reconstruct the kinetics of CDR-H3 loop dynamics and for the first time provide a method to define and localize surface plasticity upon affinity maturation.