该研究主要是通过计算机模拟，从食品来源蛋白质中预测筛选具有蛋白酶激活受体2（Protease Activated Receptor 2，PAR2）抑制作用的生物活性肽，同时预测食用藻类蛋白质酶解后所得的肽段的生物活性、水溶性等理化指标。首先，利用NCBI数据库和蛋白质晶体数据库（Protein Data Bank，PDB）比对选择食用藻类蛋白质，其次通过BIOPEP-UWM数据库模拟酶解，Peptide Ranker进行活性分析，Innovagen和ToxinPred预测高活性肽，最后采用HPEPDOCK将获得的活性评分超过0.5、水溶性优且无毒的小分子活性肽与PAR2进行分子对接模拟，以探究两者之间的分子结合能力，进而分析判别不同小分子活性肽抑制PAR2活力的潜力和机制。结果表明，小分子寡肽PAGR（-165.80）、PAR（-163.93）、IDQW（-152.95）、DISAW（-154.48）与PAR2具有较高的结合分数，是PAR2潜在的活性抑制肽。该研究旨为藻类蛋白的开发利用以及PAR2抑制剂的挖掘研究提供参考。

Computer simulations were used to predict the bioactive peptides inhibiting protease activated receptor 2 (PAR2) from food source proteins, as well as the bioactivity, water solubility, and other physicochemical parameters of the peptides obtained from the enzymatic digestion of edible algal proteins. First, edible algal proteins were selected from the NCBI database and Protein Data Bank (PDB). Thereafter, enzymatic digestion was simulated using the BIOPEP-UWM database, activity analysis was performed using Peptide Ranker, high active peptides were predicted using Innovagen and ToxinPred, and finally, HPEPDOCK was used. The obtained small active peptides with activity scores over 0.5, excellent water solubility, and non-toxicity were simulated by molecular docking using PAR2 to investigate their molecular binding ability. The potential and mechanism to discriminate different small active peptides to inhibit PAR2 activity was analyzed. The results showed that the small molecule oligopeptides PAGR (-165.80), PAR (-163.93), IDQW (-152.95) and DISAW (-154.48) exhibited high binding to PAR2 and were potential active inhibitory peptides of PAR2. The findings of this study provide valuable insights for developing and utilizing algal proteins and exploring PAR2 inhibitors.

广东省科技创新战略专项资金（2022B1212010015）；广东省基础与应用基础研究基金（2020A1515110326）；广东省市场监督管理局科研攻关项目（2022CS01）；广东省教育厅创新强校项目（2022KTSCX120）