## 3 Results and Discussion
### Interaction between Ummi Dipeptides and Homo sapiens mGluRuR1 Open-Open Conformation
Whereas DG (Ki = 294.68 uM) could bind to Ser165 and Ser186, ES (Ki = 165.54 uM) and VG (Ki = 17.44 uM) would dock with Ser165 and Asp318. It is important to note that the repeatability of some non-key residues in all dipeptide cases, such as Thr188, Gln211, Lys409, and glutamic acid-binding residues Tyr74 and Arg78, suggest more of the previously predicted in the bibliography may be implicated in the recognition of umami compounds. Since the crystallographic structures 1 EWK and 3 KS9 are available in closed-open and open-open conformation states, the differences observed on residues may be due to conformational changes [64]. Apparently, residues, such as Thr188 and Tyr74, can form both H-bonds and hydrophobic interactions. However, as in the previous cases, most interactions are due to H-bonds. In fact, AH, EE, ES, and EV presented the same number of them with slightly differences in the residues implicated, which explains the diversity of Ki values and, thus, it may illustrate the receptor specificity. It seems that in the _Rattus norgeticus_ closed-open conformation, polar acidic residues from dipeptides promote H-bonds. Salt bridges and hydrophobic connections appear to distribute differently compared to what occurred for the _Rattus norgeticus_ mGluR1 receptor. Actually, the dipeptides AH and VG would not be able to stablish salt bridges. Attending to the Ki, lower values were obtained for AH, EV, and VG. Making a comparison between the open-open conformations of _Rattus norgeticus_ and _Homo sapiens_, the most frequent and common residues that interacted with E were Tyr74 and Lys409. This last residue is also remarkable for the case of dipeptides in joint with Ser186. However, a disparity of interactions between both receptors could be perceived, indicating that various key residues implicated in the recognition of the ligands would differ between the two  
Figure 4: Two-dimensional representation of protein–ligand interactions between _Homo sapiens_ open–open conformation of mGluR1 (PDB ID: 3 KS99) and Glu (PubChem ID: 33032), AH (PubChem ID: 9837455), DA (PubChem ID: 5491963), DG (PubChem ID: 151148), EE (PubChem ID: 439500), ES (PubChem ID: 6995653), EV (PubChem ID: 6992567), VG (PubChem ID: 6993111). H bonds are shown as dashed lines, hydrophobic contacts are represented by green splines; the corresponding pocket residues are also shown in the same color. Diagrams obtained from the ProteinsPlus PoseView tool, from which E amino acid was predicted to interact with Tyr74, Arg78, Ser186, and Lys409; AH, with Ser165, Thr188, Asp208, Asp318; DA, with Ser165, Thr188, Asp318, and Lys409; DG, with Ser165, Asp208, Asp318 and Lys409; EE, with Ser165, Thr188, Asp208, and Lys409; ES, with Ser165, Thr188 and Lys409; EV, with Ser165, Thr188, Asp208, Asp318, and Lys409; and VG, with Ser165, Thr188, Asp208, and Asp318. H-bonds were estimated by PoseView to be stabilized in all cases. species although the sequence is highly conserved. Intriguingly, considering the residues predicted for the same receptor, the majority of them are repeated for each dipeptide. Indeed, the dipeptides may attach to the _Rattus norvegicus_ closed-open conformation by Tyr74, Trp110, Ser186, Thr188, Asp318, Arg323, and Lys409. Tyr74, Trp110, Ser186, Glu292, and Lys409 frequently appeared for the case of _Rattus norvegicus_ open-open conformation and Ser165, Ser186, Thr188, Gln211, Asp318, and Lys409 are remarkable attending to the _Homo sapiens_ open-open conformation. The open-open conformations from the two species generally presented lower number of H-bonds in comparison with the closed-open conformation from _Rattus norvegicus_, which probably was translated in a lower Ki value range. This may be because the conformational change to the closed form that occurred in the ligand-binding domain benefited the docking within the protomer, promoting a greater number of interactions.