甲氨蝶呤与牛血清白蛋白相互作用的光谱和分子对接研究

Study on the interactions of methotrexate with bovine serum albumin by spectroscopy and molecular modeling method

利用紫外-可见吸收光谱法、傅立叶红外光谱法和分子对接技术研究了抗癌药物甲氨蝶呤与牛血清白蛋白的相互作用。紫外光谱发现,在298 K和308 K,甲氨蝶呤与牛血清白蛋白结合常数分别为5.28×105L/mol和6.14×105L/mol,通过热力学计算得到反应的焓变和熵变。热力学函数说明甲氨蝶呤与牛血清白蛋白之间的作用力主要为疏水作用力。红外光谱表明甲氨蝶呤与牛血清白蛋白分子中氨基酸残基的硫及氮原子形成键合作用。结合AutoDock 4.2分子对接软件模拟研究了二者的键合模式和键合机制,表明甲氨蝶呤与牛血清白蛋白的相互作用力主要是疏水作用。

The interactions between the anti-cancer drug methotrexate （MTX） and bovine serum albumin （BSA） were investigated in detail by UV absorption and IR spectroscopies, combined with molecular modeling method. UV absorption spectra showed that the binding constants were 5.28×10^5L/mol（298 K） and 6. 14×10^5L/mol （308 K）, respectively. The thermodynamic parameter AH was 8. 174 KJ/mol. The thermodynamic parameters revealed that methotrexate tended to bind with BSA mainly by hydrophobic interaction. The results of IR spectroscopy showed that MTX could interact with sulfur-containing and nitrogen-containing groups in BSA molecule. Furthermore, Molecular docking was performed to reveal the possible binding mode or mechanism and suggested that methotrexate could bind strongly to BSA. The results revealed that methotrexate tended to bind with BSA mainly by hydrophobic interaction. The results were in agreement with the experimental ones.