AcSDKP与TGF-β受体1相互作用的分子对接研究

Molecular docking study on the interaction of TGF - β receptor 1 and AcSDKP

目的利用分子对接方法阐释AcSDKP及其突变体多肽与转化生长因子B（TGF-β）受体1相互作用。方法利用药物设计平台Sybyl-X2．1构建的AcSDKP及其突变体多肽的分子结构，采用Surflex分子对接方法将AcSDKP及其突变体多肽对接到TGF-β受体1中，考察它们的分子对接打分数值及相应的结合用模式。结果AcSDKP可与TGF-β受体1形成稳定的相互作用，且以氢键相互作用为主。AcSDKP的第2位氨基酸当突变为色氨酸时（即AcSWKP）具有比原型肽AcSDKP更强的TGF-β受体1结合能力。除了AcSWKP，其他突变体在与TGF-β受体1的相互作用时要弱于AcSDKP。结论AcSDKP可以与TGF-β受体1形成稳定的相互作用，说明AcSDKP可能是通过抑制TGF-β受体1来发挥其抗纤维化的生物活性。另外，分子对接方法预测AcS-DKP的突变多肽AcSWKP可能具有更强的抗纤维化活性。

Objective To investigate the interaction between TGF - β receptor 1 and （ N - Acetyl - Ser - Asp - Lys - Pro） AcSDKP through molecular docking. Methods The structures of AcSDKP and its mutations were designed and modeled using Sybyl - X2.1. Molecular docking with Surflex was adopted to elucidate the binding of AcSDKP and its mu- tations to TGF - β receptor 1. Results AcSDKP could stably interact with TGF - β receptor 1, where twelve hydrogen bonds were formed. AcSDKP also increased the binding affinity to TGF - β receptor 1 after mutation of its second residue from aspartic acid （D） to tryptophan （W）. However, other mutations on positions of second or third residues decreased binding affinities. Conclusions AcSDKP is an anti - TGF - β/Smad peptide and can specifically inhibit TGF - β re- ceptor 1. Molecular docking studies suggest that AcSDKP or AcSWDP has stronger binding interactions with TGF - β re- ceptor l, which are dominated by several hydrogen bonds.