## 3 Results and Discussion
### Interaction between Ummi Dipeptides and Homo sapiens mGluRuR1 Open-Open Conformation
Based on the results provided by the in silico prediction, it seems the Ki did not show a particular trend attending to the peptide sequence as the dipeptides with lower values were not similar when comparing the cases. However, VG was present as one of those with the lowest Ki in all three cases. There is little information reporting mechanism analyses with mGluR1. In fact, most investigations are based on the use of 1 EWK and 3 KS9 mGluRs as templates for homology modeling to simulate the docking between drugs or taste-active molecules and T1R1/T1R3 or T2R1/T1R3 [65; 66; 67; 68; 69; 70], and do not deepen the contribution of mGluRs to taste perception, although knockout studies have demonstrated that they play a key role independently of the heterodimers in umami recognition [29]. It is known that E recognition is accomplished by Tyr74, Arg78, Ser165, Ser186, Thr188, and Lys409 in both ligand-binding regions. However, residues Ser164, Asp208, Tyr236, Glu292, Gly293, Asp318, and Arg323, in the closed subunit, are implicated [62]. Some of these interactions were found in this study in both cases, but also when docking using the dipeptides as ligands. Docking simulations between 1 EWK and sweet aspartyl-dipeptide derivatives revealed similar involved residues, such as Ser186, Asp318, and Lys409 through H-bonds; Arg78, Ser186, Thr188, Asp318, and Lys409 by salt bridges and Tyr74 and Tyr236 by hydrophobic interactions. In addition, some of the derivatives were able to stablish H-bonds with Trp110 and Gln211. The carboxylate groups appear to benefit the interaction with Lys409, whereas the carbonyl group ligand derivatives, with Arg323 as benzene ring-containing derivatives can have hydrophobic interactions with residues Tyr74 and Tyr236 [40]. Eugenol, a phenolic compound found in the leaves, buds, of clove _Syzygium aromaticum_ ([PERSON], links with 3 KS9 with similar residues, such as Trp110, Ser165, and Asp318 [42]. Such predicted estimations obtained in this study, in agreement with others, indicate that umami dipeptides dock the mGluR1 active site by mimicking E, but other residues may be implicated in each particular dipeptide to stabilize the binding. Briefly, it is important to remark that these dipeptides have been previously demonstrated to exert bioactive properties. Indeed, the dipeptide AH has been registered on BioPep [71] as in vitro ACE-I and DPP-IV inhibitor and in vitro antioxidant. DA and DG can act as in vitro ACE-I inhibitors; DA can also act as in vitro DPP-III inhibitor. The dipeptide EE would act as a stimulating vasoactive substance release in human aortic endothelial cells; ES exerts in vitro DPP-IV inhibitory activity and EV and VG can be in vitro ACE and DPP-IV inhibitors. More recently, dipeptides EE, ES, and DA have been tested for their anticholesterolemic activity obtaining values of 47.2, 45.5, and 49.6% of HMG-CoA inhibitory activity, respectively, at 1 mM [72]. On the other hand, as mentioned above, mGluR1 has been found in the stomach [27]. Specifically, it has been located at the apical membrane of chief cells and possibly in parietal cells in a rat glandular stomach. A diet with 1% E amino acid in rats was reported to induce changes in the expression of pepsinogen C and gastric intrinsic factor mRNAs in stomach mucosa [73], which suggests that mGluR1 is involved in the gastric phase regulation of protein digestion [74]. Other genes affected by E supplementation were serotonin receptor 3A (_Htr3a_), nitric oxide synthase 3 (_Nos3_), phospholipase type C-\(\beta\)1 (_Plcb2_), and transient receptor potential cation channels _Trp1_ and _Trpm5_. The last three are related to the mGluR1 signal transduction cascade [73]. In addition, activation of mGluR1 modulates gastric vagal afferents from the luminal side, releasing mucin and nitrite mono-oxide, which stimulates serotonin (5 HT) release at the enterochromaffin cell. Finally, this 5 HT stimulates 5 HT3 receptor at the nerve end of the vagal afferent fiber.