Ligand-induced domain movement in an antibody Fab: molecular dynamics studies confirm the unique domain movement observed experimentally for Fab NC6.8 upon complexation and reveal its segmental flexibility

Two molecular dynamics simulations were carried out for the antibody Fab NC6.8, both with and without the guanidinium sweetener ligand NC174, in order to assess the segmental flexibility as well as the conformational changes upon ligand binding. Trajectory analyses of the simulation of the uncomplexed Fab suggest low-amplitude motions of the Ig domains with respect to each other, most clearly reflected by a periodic alteration of the elbow angle within a range of 11 degrees. Upon insertion of the hapten into the binding site, the quaternary structure of the Fab exhibits considerable rearrangements: the elbow angle changes by almost 30 degrees, the light chain is elongated and the heavy chain becomes more flexed. Comparison with experiment reveals some interesting agreements with X-ray crystallographic results published previously.