癌胚抗原低亲和力表位改造中的分子对接

Molecular docking simulations of low-affinity CTL epitopes and its analogue derived from carci- noembryonic antigen

目的通过分子对接方法筛选表位改造后的高亲和力CTL表位。方法在图形工作站上,将癌胚抗原来源的低亲和力表位及其N末端第一位残基以酪氨酸替换后的突变体,分别与MHCⅠ类分子进行对接,对接所得最佳构象进行600ps分子动力学模拟修正。结果改造后的突变体与MHC分子间存在较强的氢键和疏水相互作用,组成肽结合槽口袋A的残基Tyr7、Tyr171和Tyr159与多肽N末端形成稳定的氢键作用网络,并且P1位酪氨酸上的苯环可与Trp167上的苯环发生ππ堆积作用。结论分子对接模型预测的肽MHC复合物作用模式,提示改造后的突变体与MHCⅠ类分子间具有更高的亲和力,与实验结果一致。

Objective To screen high-affinity peptide analogs of CTL epitopes by molecular docking. Methods Low-affinity CTL epitope derived from carcinoembryonic antigen （CEA） and its analogue （by replacing the amino acid at position 1 with a tyrosine） were docked respectively with MHC class Ⅰ molecule, followed by 600 ps molecular dynamics simulations. Results More powerful H-bonding interaction and hydrophobic interaction were found between the analogue and the MHC class Ⅰ molecule. Tyr7, Tyr171, and Tyr159 of pocket A within the binding cleft could form a network of hydrogen bonds that directly interacted with the peptide N-terminus. Moreover, there was a π-π stacking interaction between Trp167 and the aromatic P1 residues. Conclusion All these results strongly suggest that the analogue has higher affinity to MHC molecule, which is in good agreement with the experimental data.