Agonist-specific vibrational excitation of glutamate receptor

Conformational changes of receptors are dominated by the excitation of their collective motions. The most likely energy source of this excitation is considered to be a collision of an agonist with the binding site of a receptor and a consequential excitation of their vibrational modes. In the present study, as an approach to elucidating the mechanism for receptor activation, we chose both the symmetric stretching vibration of the 1C-carboxyl group of glutamate and the bending vibration of the guanidinium group of Arg485 of the glutamate receptor subunit GluR2 based on our previous study, and we quantum-mechanically calculated the vibrational excitation probability of these two vibrations by glutamate collision. The excitation probability of these two vibrations was found to exceed 0.5 about 260 fs after the onset of collision within the first-order perturbation approximation. Taking into account that the period of these vibrations is about 20 fs, we can expect that the vibrational excitation occurs in Arg485 after tens of vibrations during the collision. This vibrational energy may redistribute to the collective motions of the receptor, resulting in global conformational changes in the receptor. We also confirmed that the charge transfer was small between an agonist and the binding site of GluR2. The glutamate receptor may be oscillatory systems that require the energy injection into the specific vibrational modes of the specific amino acid residues to trigger their activation. Such an injection of energy is provided by agonist collision.