State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315211, Zhejiang, China.
Department of Chemistry, Tsinghua University, Beijing, 100084, PR China; Institute of Drug Discovery Technology, Ningbo University, Ningbo, 315211, China.
Biomaterials. 2022 Sep;288:121697. doi: 10.1016/j.biomaterials.2022.121697. Epub 2022 Aug 6.
To shorten the complex and tedious process of traditional umami peptide identification, a novel model based on common feature pharmacophore (HipHop, a ligand molecule-based screening method) and molecular docking (a receptor protein-based screening method) was established for umami peptide screening. In this study, HipHop was used to perform a preliminary screening of peptides. Dipeptides with potential umami activity were docked into the umami taste receptor T1R1/T1R3 for a second screening. Twenty previously unreported umami dipeptides identified through virtual screening were validated using sensory evaluation and electronic tongue analysis. All 20 dipeptides (HE, HD, KE, EH, ET, EQ, DH, DR, DQ, DN, DY, DM, DI, DV, QE, QD, NE, ND, CE, and SE) had umami taste with umami threshold values ranging from 0.094 to 1.517 mmol/L. Therefore, when we increased the screening criteria for docking energy to -60 kcal/mol, the virtual screening results had 100% accuracy. The T1R1-peptide complexes of the four dipeptides with the lowest umami threshold values were subjected to molecular dynamics (MD) simulations for 100 ns, and the results showed that the four umami dipeptides remained in the starting active cavity. Overall, this screening strategy could be applied to the rapid screening of umami peptides in food products.
为了缩短传统鲜味肽鉴定过程的复杂性和繁琐性，建立了一种基于常见特征药效团（HipHop，一种基于配体分子的筛选方法）和分子对接（一种基于受体蛋白的筛选方法）的鲜味肽筛选新模型。在这项研究中，使用 HipHop 对肽进行初步筛选。具有潜在鲜味活性的二肽被对接进入鲜味味觉受体 T1R1/T1R3 进行二次筛选。通过感官评价和电子舌分析验证了通过虚拟筛选鉴定的 20 种以前未报道的鲜味二肽。所有 20 种二肽（HE、HD、KE、EH、ET、EQ、DH、DR、DQ、DN、DY、DM、DI、DV、QE、QD、NE、ND、CE 和 SE）均具有鲜味，鲜味阈值范围为 0.094 至 1.517 mmol/L。因此，当我们将对接能的筛选标准提高到-60 kcal/mol 时，虚拟筛选结果的准确率达到 100%。四种鲜味阈值最低的二肽的 T1R1-肽复合物进行了 100 ns 的分子动力学（MD）模拟，结果表明四种鲜味二肽仍保持在起始活性腔中。总的来说，这种筛选策略可应用于食品中鲜味肽的快速筛选。
