白啤中二肽基肽酶-IV抑制肽的虚拟筛选及活性分析

以青岛白啤作为研究对象，建立一种快速筛选二肽基肽酶-IV（dipeptidyl peptidase-IV，DPP-IV）抑制活性肽的方法。白啤经超高效液相色谱-四极杆-静电场轨道阱高分辨质谱结合De novo软件鉴定出肽段序列，确定了置信度较高的68 条肽段。应用Peptide Ranker对68 条肽段进行生物活性评分，筛选出评分大于0.5的4 条肽段，同时又根据先前文献对抑制DPP-IV活性肽的氨基酸位点研究报道，筛选出13 条肽段。对筛选出的17 条肽段进行吸收、代谢及毒性预测及分子对接评价，选定了VPFPHTP和LAKLQR两条潜在抑制DPP-IV活性肽段。通过肽段与DPP-IV分子对接构象图表明，选定的2 条活性肽均能以氢键及疏水作用紧密结合DPP-IV，从而抑制其活性。利用体外方法验证2 条活性肽抑制DPP-IV活性，结果显示2 条肽段具有明显的DPP-IV抑制活性。

Virtual Screening of Activity Evaluation of Dipeptidyl Peptidase-IV Inhibitory Peptides in White Beer

This study aimed to establish a method for rapid screening of dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides from white beer. The amino acid sequences of polypeptides were identified by ultrahigh performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-MS2) with the De novo software. In total 68 polypeptides were determined with high confidence, and their biological activity was evaluated using Peptide Ranker. Of these, four were selected for their scores greater than 0.5 to predict their potential DPP-IV inhibitory activity. Meanwhile, another 13 peptides with DPP-IV inhibitory activity were selected according to previous reports. The absorption, metabolism and toxicity of these 17 peptides were predicted and they were evaluated by molecular docking. Finally, two potential DPP-IV inhibitory peptides, VPFPHTP and LAKLQR, were selected. The molecular docking results showed that both peptides could bind DPP-IV tightly by hydrogen bonding and hydrophobic interaction. The peptides were found to have obvious in vitro DPP-IV inhibitory activity.