仿刺参胶原蛋白源二肽基肽酶抑制肽虚拟筛选及分子对接研究

目的 采用生物信息学和分子对接方法筛选仿刺参胶原蛋白来源的二肽基肽酶(dipeptidyl peptidase-Ⅳ,DPP-Ⅳ)抑制肽。方法 以仿刺参胶原蛋白序列为对象，进行生物信息学分析和计算机辅助虚拟酶解,基于生物毒性、致敏性、水溶性及吸收、分配、代谢、排泄及毒性(absorption,distribution,metabolism,excretion,toxicity,ADMET)预测,筛选得到6条具有潜在生物活性的寡肽,氨基酸序列分别为CD、CQ、CS、GR、SM、MDG,进一步通过分子对接分析肽段与DPP-Ⅳ的结合活性,并分析其结合位点及方式。结果 生物信息学分析表明仿刺参胶原蛋白是生物活性肽的潜在优良来源,经木瓜蛋白酶、碱性蛋白酶及模拟胃肠道虚拟水解后能够释放出DPP-Ⅳ抑制肽;分子对接表明俩条新肽段CS、SM通过氢键、疏水相互作用分别与DPP-Ⅳ的S1、S2活性口袋结合。结论 本研究提供了一种快速筛选刺参胶原蛋白中DPP-Ⅳ抑制肽的方法。

Virtual screening and molecular docking of dipeptidyl peptidase-IV inhibitory peptides derived from collagen of Apostichopus japonicus

Objective To screen the dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides derived from Apostichopus japonicus (A. japonicus) collagen by the bioinformatics and molecular docking method. Methods The sequence of A. japonicus collagen was analyzed and virtual enzymolysised by bioinformatics in silico. Based on the prediction of biological toxicity, sensitization, solubility, absorption, distribution, metabolism, excretion, and toxicity (ADMET), 6 oligopeptides with potential biological activity were screened out, and their amino acid sequences were CD, CQ, CS, GR, SM, and MDG, respectively. In addition, the binding activity of these peptides with DPP-IV were further analyzed by molecular docking, and their binding sites and binding modes were analyzed. Results Bioinformatics analysis showed that A. japonicus collagen was a potential excellent bioactive peptides source, after hydrolyzed by papain, subtilisin, and simulated gastrointestinal digestion, DPP-IV inhibitory peptides could released. The results of molecular docking indicated that 2 new peptides CS and SM could bound to S1 and S2 active pockets of DPP-IV with hydrogen bondings and hydrophobic interactions, respectively. Conclusion This study provids a method to quickly screen DPP-IV inhibitory peptides from A. japonicus collagen.