Predicting CDR Flexibility in Immunoglobulin

While it is known that protein flexibility plays a significant role in protein folding, protein-ligand interactions, catalysis, and molecular recognition, only a few techniques are capable of quantifying immunoglobulin flexibility while less is known about immunoglobulin motions. Floppy Inclusion and Rigid Substructure Topography (FIRST) can be used to measure protein flexibility and this technique has been used to analyze immunoglobulin segmental flexibility and flexibility in the six complementarity-determining-regions. IgG2A was examined in FIRST and found to be compatible with known immunoglobulin segmental flexibility. Also, eight immunoglobulin Fab fragments were analyzed using FIRST. Specifically, it was observed that all of the light chain CDR1 loops were flexible while all of the light chain CDR2 loops were rigid. The overall results also reflect the diversity in immunoglobulin antigen recognition that is important for other immunological research, such as drug design.