为探究脯氨酸(Pro)/谷氨酸(Glu)二肽与鲜味受体分子相互作用，本研究合成了12个Pro/Glu二肽，以感官评价为基础，利用同源建模、分子对接技术研究Pro/Glu二肽与味觉受体第一家族亚型1（T1R1）、味觉受体第一家族亚型3（T1R3）和钙敏感受体(CaSR)的分子作用机制。结果表明：Pro二肽整体呈鲜效果优于Glu二肽，丝氨酸-脯氨酸（Ser-Pro）、丙氨酸-脯氨酸（Ala-Pro）、脯氨酸-丙氨酸（Pro-Ala）、脯氨酸-缬氨酸（Pro-Val）、γ-谷氨酸-蛋氨酸（γ-Glu-Met）和甘氨酸-谷氨酸（Gly-Glu）具有较强鲜味。T1R1、T1R3和CaSR模型分别有99.13%、98.07%、99.12%的氨基酸处于合理区，Pro/Glu二肽与T1R1的关键结合位点为Asp147、Thr149、Ser172和Arg277，T1R1是Glu二肽呈鲜的重要受体；与T1R3的关键结合位点为Glu45、Ser147、Val277和His278，且Ser147是N-γ-Glu二肽与T1R3受体的关键结合位点；与CaSR的关键结合位点为Leu173、Asn176、Gln179、Arg220、Ser244和Asp275，Glu二肽比Pro二肽更易与CaSR受体结合。二肽与受体主要通过氢键与疏水相互作用结合，呈味较强的二肽在对接时多嵌于受体结合口袋深处；而呈味较弱的二肽有的位于结合口袋较浅的位置，有的其疏水区或亲水区暴露于受体表面。本研究阐明了Pro/Glu二肽与鲜味受体相互作用机制，为深入研究鲜味肽呈鲜机理奠定基础。

In order to explore the molecular interaction between Pro/Glu dipeptides and umami receptors, 12 Pro/Glu dipeptides were synthesized. Based on sensory evaluation, homology modeling and molecular docking technique were used to study the molecular interaction mechanism of Pro/Glu dipeptides with umami receptors Taste receptor type 1 (T1R1), Taste receptor type 3(T1R3) and calcium-sensing receptor (CaSR). The results indicated that the overall umami effect of Pro dipeptides was better than that of Glu dipeptides, Ser-Pro, Ala-Pro, Pro-Ala, Pro-Val, γ-Glu-Met and Gly-Glu were the dipeptides with strong umami. 99.13%, 98.07% and 99.12% of the amino acids in T1R1, T1R3 and CaSR models were in reasonable regions respectively. Asp147, Thr149, Ser172 and Arg277 were the key binding sites of Pro/Glu dipeptides to T1R1which was the key receptor of Glu dipeptides. Glu45, Ser147, Val277 and His278 were the key binding sites to T1R3, and Ser147 was the key binding site between N-γ-Glu dipeptides and T1R3 recrptor. Leu173, Asn176, Gln179, Arg220, Ser244 and Asp275 were the key binding sites to CaSR, and Glu dipeptides were easier to bind to CaSR receptor than Pro dipeptides. The binding between Pro/Glu dipeptides and receptors were mainly through hydrogen bond and hydrophobic interaction. When docking, dipeptides with strong umami were mostly embedded in the depth of the receptor binding pocket, and dipeptides with weak umami were located in the shallow position of the binding pocket and some of their hydrophobic or hydrophilic regions were exposed to the surface of the receptors. Our study elucidated the interaction mechanism between Pro/Glu dipeptides and umami receptors, and laid the foundation for further study of the mechanism of umami peptides.

国家自然科学基金项目（面上项目）