  This chapter describes the application of constrained geometric simulations
for prediction of antibody structural dynamics. We utilize constrained
geometric simulations method FRODAN, which is a low computational complexity
alternative to Molecular Dynamics (MD) simulations that can rapidly explore
flexible motions in protein structures. FRODAN is highly suited for
conformational dynamics analysis of large proteins, complexes, intrinsically
disordered proteins and dynamics that occurs on longer biologically relevant
time scales which are normally inaccessible to classical MD simulations. This
approach predicts protein dynamics at an all-atom scale while retaining
realistic covalent bonding, maintaining dihedral angles in energetically good
conformations while avoiding steric clashes in addition to performing other
geometric and stereochemical criteria checks. In this chapter, we apply FRODAN
to showcase its applicability for probing functionally relevant dynamics of
IgG2a, including large amplitude domain-domain motions and motions of
complementarity determining region (CDR) loops. As was suggested in previous
experimental studies, our simulations show that antibodies can explore a large
range of conformational space.
