In this study, Qula casein derived from yak milk casein was hydrolyzed using a two-enzyme combination approach, and high angiotensin I-converting enzyme (ACE) inhibitory activity peptides were screened by quantitative structure–activity relationship (QSAR) modeling integrated with molecular docking analysis. Hydrolysates (<3 kDa) derived from combinations of thermolysin + alcalase and thermolysin + proteinase K demonstrated high ACE inhibitory activities. Peptide sequences in hydrolysates derived from these two combinations were identified by liquid chromatography–tandem mass spectrometry (LC-MS/MS). On the basis of the QSAR modeling prediction, a total of 16 peptides were selected for molecular docking analysis. The docking study revealed that four of the peptides (KFPQY, MPFPKYP, MFPPQ, and QWQVL) bound the active site of ACE. These four novel peptides were chemically synthesized, and their IC₅₀ was determined. Among these peptides, KFPQY showed the highest ACE inhibitory activity (IC₅₀ = 12.37 ± 0.43 μM). Our study indicated that Qula casein presents an excellent source to produce ACE inhibitory peptides.

中文翻译：

---

定量构效关系建模与分子对接分析从二酶联合水解获得的库拉酪蛋白水解产物中筛选血管紧张素I转化酶抑制肽

在这项研究中，from牛乳酪蛋白的库拉酪蛋白通过两种酶组合方法进行水解，并通过结合分子对接的定量结构-活性关系（QSAR）模型筛选了高血管紧张素I转化酶（ACE）抑制活性肽。分析。从嗜热菌素+碱性蛋白酶和嗜热菌素+蛋白酶K的组合产生的水解产物（<3 kDa）表现出很高的ACE抑制活性。通过液相色谱-串联质谱法（LC-MS / MS）鉴定了从这两种组合得到的水解产物中的肽序列。根据QSAR建模预测，总共选择了16种肽进行分子对接分析。对接研究表明，四种肽（KFPQY，MPFPKYP，MFPPQ和QWQVL）结合了ACE的活性位点。确定₅₀。在这些肽中，KFPQY显示出最高的ACE抑制活性（IC ₅₀ = 12.37± 0.43μM ）。我们的研究表明，古拉酪蛋白为产生ACE抑制肽提供了极好的来源。