Nε羧甲基赖氨酸靶向清道夫受体CD36的分子对接研究

Molecular docking in Nεcarboxymethyl lysine targeting scavenger receptor CD36

目的观察Nε羧甲基赖氨酸(Nεcarboxymethyl lysine,CML)是否与清道夫受体CD36具有良好的分子对接,形成稳定的相互作用。方法使用免疫共沉淀技术研究CML和CD36相互作用,采用AutoDock 4.2、iBabel及XQuartz-2.7.7软件计算CD36与CML的结合模式和亲和力。结果免疫共沉淀显示,抗CD36抗体磁珠能够沉淀出RAW264.7细胞总蛋白中的CD36,通过抗CML抗体能检测出与CD36结合的CML。选择小分子化合物CML与最优的CD36胞外段4Q4B蛋白结构进行对接分析显示,化合物CML与CD36胞外段4Q4B蛋白结构的亲和力为-29.62kJ/mol。CML可占据4Q4B结合口袋开口的1/2左右,ARG82、ASN71和THR70为受体互作氨基酸。进一步的对接分析显示,CML可以与4Q4B形成3个相互作用的氢键,对接预测抑制常数6.92,均方根偏差2.54。结论 CML与CD36胞外段4Q4B蛋白结构具有较好的对接,可形成稳定的相互作用,氢键是主要的相互作用方式。

Objective To study whether Nε carboxymethyl lysine(CML)can form a good molecular docking with the scavenger receptor CD36 and induce a stable interaction.Methods The interaction between CML and CD36 was studied by co-immunoprecipitation.The binding mode and affinity of CD36 to CML were tested using AutoDock 4.2,iBabel and XQuartz-2.7.7 software respectively. Results Co-immunoprecipitation showed that anti-CD36 antibody magnetic bead could precipitate CD36 from the total protein in RAW264.7 cells and anti-CML could detect CD36 binding CML.CD36 had a good molecular docking with CML,CD36 and CML interacted stably with each other.The affinity of CML to 4Q4B protein structure of CD4 extracellular domain was -29.62 kJ/mol.ARG82,ASN71 and THR70 were the products of amino acid receptor interaction. Further docking analysis showed that CML could form 3 interacting hydrogen bonds with 4Q4B,and the docking prediction inhibition constant was 6.92 with a root mean square deviation of 2.54 A.Conclusion A good molecular docking between CML and 4Q4B protein structure of CD36 extracellular domain can induce a stable interaction between CML and CD36.Hydrogen bonding is the main interaction mode.