Hypertension is nowadays one of the major world concerns in public health. Several food proteins, among which caseins, can be substrates for generating peptides with antihypertensive potential. With the increasingly evolution of computational tools, in silico molecular modeling have gained prominence in studies of protein-ligand complexes in different research fields, such as pharmaceutics and biochemical engineering. However, the application of such methodologies in food-related research can be considered still embryonic. Thus, the central aim of the present work was to apply molecular modelling in order to elucidate the molecular bases of the anti-hypertensive potential of milk caseins-derived peptides. Firstly, hydrolysates obtained from a controlled trypsinolysis of caseins were fractioned according to their molecular weight, by ultrafiltration and RP-HPLC. The obtained fractions were evaluated with regard to their in vitro inhibitory angiotensin-converting enzyme activity (%I_ACE). Six chromatographic fractions were identified, and three of them displayed high ACE-inhibition (F₁: 80.68%; F₂: 79.00%; and F₄: 62.44%). Finally, intermolecular interactions networks in complexes formed between ACE and the identified peptides were assessed through in silico molecular docking. At the molecular level, a correlation between in vitro and in silico results was found: the peptides FFVAPFPEVFGK (F₆), FALPQYLK (F₂, F₄) and ALNEINQFYQK (F₁) presented the lowest biding energies and interacted by specific H-bonds, electrostatic and hydrophobic interactions formed within ACE active site S1 residues (Ala354, Glu384, and Tyr 523) and the Zn²⁺ coordinated residues (His383, His387, and Glu411). The fraction F₃, despite its low total peptide concentration, presented a moderate inhibitory activity for ACE (49.2%), likely due to H-bonds between HQGLPQEVLNENLLR and the active site S1 residues.

中文翻译：

---

酪蛋白衍生的具有降压潜力的肽：通过分子对接研究生产，鉴定和评估与血管紧张素I转换酶（ACE）形成的复合物

如今，高血压已成为世界上主要的公共卫生问题之一。几种食物蛋白（其中酪蛋白）可以作为产生具有降压潜力的肽的底物。随着计算工具的不断发展，计算机分子建模在不同研究领域（例如制药学和生化工程学）中对蛋白质-配体复合物的研究中日益突出。但是，这种方法在食品相关研究中的应用仍被认为是萌芽的。因此，本工作的主要目的是应用分子模型，以阐明酪蛋白酪蛋白衍生肽抗高血压潜力的分子基础。首先，根据酪蛋白的分子量，对酪蛋白进行受控的胰蛋白酶消化，然后将其水解物分馏，通过超滤和RP-HPLC。评估所得级分的体外抑制血管紧张素转化酶活性（％I_ACE）。鉴定出六个色谱级分，其中三个显示出较高的ACE抑制率（F ₁：80.68％； F ₂：79.00％； F ₄：62.44％）。最后，通过计算机分子对接评估了ACE与已鉴定肽之间形成的复合物中的分子间相互作用网络。在分子水平上，发现了体外和计算机模拟结果之间的相关性：肽FFVAPFPEVFGK（F ₆），FALPQYLK（F ₂，F ₄）和ALNEINQFYQK（F ₁）呈现最低的出价能量，并通过特定的H键，ACE活动位点S1残基（Ala354，Glu384和Tyr 523）和Zn ²⁺配位残基（His383，His387和Glu411）内形成的静电和疏水相互作用相互作用。尽管馏分F _3的总肽浓度低，但对ACE的抑制作用中等（49.2％），这可能是由于HQGLPQEVLNENLLR和活性位点S1残基之间的H键所致。