Investigation of structural suitability of agmatine with glutamatergic ion channels: Molecular docking study

Aim: Agmatine is considered a neurotransmitter that is expressed almost everywhere in the brain and is thought to act as a neuromodulator. There is evidence that it interacts with glutamatergic ion channels associated with physiological and pathological states such as excitability and hyperexcitability. In this study, possible relationships of seizure-related ion channels (KARs, AMPARs and NMDARs) with agmatine are discussed using molecular docking method. Material and Method: Information on glutamatergic ion channels was obtained from the Protein Data Bank. The 2D structure of agmatine and inhibitors of receptors were retrieved from NCBI PubChem in .sdf format. Simulation studies were carried out using the Auto Dock 4.2.6 software program. Results: Binding sites were determined. The binding energy of agmatine to these receptors was compared with reference molecules. In this case, the binding energy of agmatine to KAR, AMPAR and NMDARs is -5.73 kcal/mol, -5.41 kcal/mol and -4.01 kcal/mol, respectively. In addition, when compared with the binding energies of the glutamate molecule, approximate energy values were obtained. Conclusion: In conclusion, it can be said that Agmatine does not have the ability to structurally block the ionotrophic glutamate receptors AMPAR, KAR and NMDAR as a result of its weak bonds. However, it seems to have the ability to bond to the channel with binding energies close to glutamate binding. We think that agmatine binds to the receptor at the glutamate binding site, but instead of activating the receptor, it may have prevented the receptor from being activated by blocking the binding of glutamate.