基于分子对接虚拟筛选含酪氨酸残基的ACE抑制三肽

Virtual Screening of ACE Inhibitory Tripeptides Containing Tyrosine Residues Based on Molecular Docking

为获得含酪氨酸残基的ACE抑制三肽,借助在线Novopro数据库构建C端为酪氨酸的三肽进行虚拟筛选,得到具有ACE-C结构域选择性抑制的三肽,预测其生物活性、水溶性、肠胃吸收性、代谢和毒性等性质,运用分子对接计算出与血管紧张素转化酶(angiotensin-I converting enzyme,ACE)具有高度亲和力的四种ACE抑制肽RWY、FRY、YRY和RFY并进行体外ACE抑制活性测定,探讨结合位点与作用关系。结果表明,经筛选得到的四种三肽RWY、FRY、YRY、RFY具有明显的ACE抑制活性,IC_(50)值分别为228.67、113.10、272.61、101.00μmol/L。分子对接虚拟结果显示,RWY、FRY、YRY、RFY均与S_(1)′口袋高度亲和,产生氢键相互作用,其中与S_(1)′口袋结合产生2条氢键的RFY的抑制效果最佳。本文利用生物信息学原理,针对性筛选ACE-C结构域选择性抑制的酪氨酸三肽,为ACE抑制肽的高速筛选提供新的可能性。

In order to obtain ACE inhibitory tripeptides containing tyrosine residues,the online Novopro database was used to construct tripeptides with tyrosine at the C-terminus for virtual screening to obtain tripeptides with selective inhibition of ACE-C domains,and predict their biological activity,water solubility,gastrointestinal absorbability,metabolism,and toxicity and other properties.The four ACE inhibitor peptides with high affinity to angiotensin-converting enzyme(ACE)were calculated by molecular docking,and the in vitro ACE inhibitory activity was determined to explore the relationship between binding sites and effects.The results showed that the four selected tripeptides RWY,FRY,YRY,and RFY had significant ACE inhibitory activity,with IC_(50) values of 228.67,113.10,272.61,and 101.00μmol/L,respectively.The virtual results of molecular docking showed that RWY,FRY,YRY,and RFY all had high affinity with S1'pocket and produce hydrogen bond interactions.Among them,RFY combined with S_(1)'pocket to produce two hydrogen bonds had the best inhibitory effect.This article used bioinformatics principles to screen tyrosine tripeptides selectively inhibited by the ACE-C domain,providing new possibilities for high-speed screening of ACE inhibitor peptides.