Ionotropic glutamate receptors (iGluR), classified as NMDA, AMPA or kainite receptors on the basis of their pharmacological properties, are ligand-gated ion channels that mediate the major excitatory synaptic signals in the central nervous system. Seminal X-ray crystallographic studies have established that the two lobes of the extra-cellular ligand-binding domain of these receptors move as rigid-domains as they close in around the ligand in a Venus fly trap like mechanism. The degree of closure has been correlated with the efficacy of the ligand. But the structure of some functional states of these receptors, such as the desensitized state (a state in which the receptor no longer is active although the ligand is still bound), remain unknown. With the long-term objective of obtaining a structural context for the desensitized state of non-NMDA ionotropic glutamate receptors, we have undertaken a systematic study of the conformational dynamics of the AMPA receptor iGluR2 and the kainate receptor iGluR6. We report the results of Molecular Dynamics simulations of the apo and holo-forms (glutamate bound) for the iGluR2 and iGluR6 receptors in their isolated state and in their dimer state (iGluR receptors are dimers of dimers). The results of these computational studies indicate the existence of several rigid-domain motions that modify the interface between the two lobes of the ligand-binding domain. The functional significance of these motions is addressed by combining bioinformatics approaches with in-silico mutational analyses that can serve as the basis for an experimental validation of the identified molecular mechanisms for these motions.