关键词: 血管紧张素转换酶抑制肽, 卵清蛋白, 多级虚拟筛选, 半胱氨酰-异亮氨酰-赖氨酸, 药效团模型

Abstract: The present study aimed to characterize potent angiotensin converting enzyme (ACE) inhibitory peptides from ovalbumin. Ovalbumin was in silico cleaved by gastrointestinal proteases. Subsequently, the toxicity, solubility, and absorption, distribution, metabolism, and excretion (ADME) properties of the tripeptides were predicted, and out of these, tripeptides strongly bound to ACE were selected and their activity was confirmed. As a result, a novel ACE inhibitory tripeptide CIK with IC50 value of (161 ± 0.06) μmol/L was identified. CIK-ACE complex was stabilized by 5 conventional hydrogen bonds, 2 carbon hydrogen bonds, and 4 salt bridges. The best docking poses of CIK could bind with the amino acid residues of ACE Gln281, His353, Ala354, Glu376, Val380, His383, Glu384, Lys511, His513, Tyr523, and Phe527. The best pharmacophore model was generated consisting of three hydrogen bond acceptors, one hydrophobic region, and one positive ionizable center, and four features were matched with the tripeptide CIK.

Key words: angiotensin converting enzyme inhibitory peptides, ovalbumin, multistep virtual screening, Cys-Ile-Lys, pharmacophore model