Figure 2.

Free energy surfaces of the CDR-H3 loop in a combined coordinate system of all investigated anti-MET Fab variants, sorted by descending bispecific IgG yield. The crystal structure of the Parent (PDB accession code: 4K3J) is projected into the free energy landscape and depicted as white dot. The percentages in the heading refer to the experimentally determined bispecific yields for the anti-MET Fab variants, respectively. Conformational spaces of the CDR-H3 loop ensembles showing a substantial population shift of the CDR-H3 loop from the binding competent state toward a side minimum resulting in a drop in bispecific IgG yield.