Investigating the Mechanism of Kainate Receptor and Identifying its Inhibitors Using In-Silico Techniques

The GluK1 receptor, an ionotropic glutamate receptor, operates as a ligand-gated ion channel. Opioids stand as the most potent pain-relieving medications currently prescribed in the medical field. Inhibiting this receptor is anticipated to result in a reduction of dopamine release in the Nucleus Accumbens, effectively preventing the primary factor contributing to addiction. In addition, in the absence of the glutamate, the GluK1 receptor cavity should shrink and expand in the presence of it. We hypothesized that the glutamate binding and unbinding in the receptor cavity should result in major conformational changes (cavity opening and closing activity) in the glutamate binding site. In the current research, we utilized computational techniques, specifically molecular dynamics simulations, to initiate an examination of the GluK1 receptor and its mechanism for binding with glutamate. Additionally, we employed molecular docking methods to predict compounds capable of binding to the glutamate binding site, potentially inhibiting this receptor. Our simulations have highlighted that the primary fluctuations within the receptor predominantly occur during glutamate binding. Lastly, we have also proposed a mechanism for how glutamate binds to the receptor.