Non-competitive N-methyl-D-aspartate (NMDA) receptor (NR2B) structure in complex with antidepressant arketamine

The present research study relates to investigation of the electronic properties of the novel medicinal compound arketamine as a treatment of major depressive disorder using density functional theory (DFT) method. In first step, the molecular structure of the title compound is optimized at B3LYP/6-311++G(d,p) level of theory at room temperature. Then, its stability and reactivity properties are calculated by frontier molecular orbitals (FMOs) energies. The global reactivity indices show this medicinal molecule is a more stable compound and has low reactivity.On the other hand, the docking analysis of the ligand-receptor complex shows the steric interactions play the main role in this complex formation. Also, the data shows the NR2B residues containing Gly [A] 128, His [A] 127, Tyr [A] 282, Gly [A] 264, Asp [A] 265, Met [A] 132 and Ser [A] 131 are the major amino acids participating in the arketamine-NR2B complex formation. In overall, the results of molecular docking analysis show an intermediate affinity to NR2B subunit of NMDA receptor.