ACEC-结构域选择性抑制二肽与ACE结构域的结合模式

IW(Ile-Trp)、VW(Val-Trp)是两种对人体体细胞ACE(somatic ACE,s ACE)中的C-结构域(C-domain)具有选择抑制性活性的食源性二肽,但其与ACE两个结构域(包括C-domain和N-domain)的结合模式与分子机制尚不明确。本实验采用分子柔性对接技术分别对上述两种肽与靶标的作用位点、结合能及作用力类型等进行研究。对接结果表明,IW、VW与ACE C-domain的活性位点存在氢键、亲水、疏水相互作用力及配位键,与N-domain作用模式相似,但生成氢键数目较少,且与Zn~(2+)不产生静电相互作用。通过比较IW、VW分别与两个结构域结合的能量差异,证明IW、VW针对两个结构域有不同的抑制强度,可为指导开发ACE C-domain选择性抑制肽提供理论参考。

Binding Modes between C-Domain Selective Angiotensin-Converting Enzyme (ACE) Inhibitory Dipeptides and ACE Domains

The C-domain selective angiotensin-converting enzyme (ACE) inhibitory activities of food-derived dipeptides, including Ile-Trp (IW) and Val-Trp (VW), were recently verified by experiments. However, their interaction modes with the C-domain and N-domain of ACE and the molecular mechanism remain unclear. In the present study, flexible molecule docking technology was used to elucidate the active sites, interaction energy and intermolecular force types between the peptides and ACE. The results demonstrated that hydrogen bond, hydrophilic, hydrophobic and electrostatic interactions, and coordinate bond existed between the active pockets of the C-domain and IW and VW. The interaction of the N-domain with the peptides was similar to that of the C-domain, which had fewer hydrogen bonds and no electrostatic interactions. By calculating the binding energy difference between the two domains, we could seek the theoretical support for the different inhibitory potency of IW and VW. The above information will be helpful for the development of C-domain selective ACE inhibitory peptides.