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 F ab NC6.8, both with and without the guanidinium sweetener ligand NC174 , in order to assess the segmental flexibility as well as the conforma tional changes upon ligand binding. Trajectory analyses of the simulat ion of the uncomplexed Fab suggest low-amplitude motions of the Ig dom ains with respect to each other, most clearly reflected by a periodic alteration of the elbow angle within a range of 11 degrees. Upon inser tion 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 interest ing agreements with X-ray crystallographic results published previousl y. (C) 1998 Academic Press Limited.