Pepsin is an aspartic protease that is involved in the digestion of food in the stomach of mammals. Continuous and long-term use of therapeutic agents will cause chronic contact of the drug with pepsin, and as a result, the structure and function of enzyme may change. In this regard the interactions of isoniazid and rifampin as the first line treatments of tuberculosis with pepsin were investigated by various methods such as fluorescence spectroscopy, FTIR, molecular docking and molecular dynamics simulation. Based on the results obtained in this study, the mentioned drugs can form stable complexes with pepsin and the structure of protein changes slightly. According to the results, the major forces in the formation of the protein-drug complex are electrostatic and hydrophobic forces for isoniazid and rifampin respectively and isoniazid shows to form a stronger binding with protein. The FTIR spectrum of the protein shows that little change was occurred in the structure of pepsin in the presence of the drugs. Molecular modeling results of the binding of isoniazid and rifampin to the pepsin confirm laboratory results and show that the binding site of drugs is close to the active site of the enzyme. Also, the activity of pepsin in the presence of both drugs has significantly increased.

胃蛋白酶是一种天冬氨酸蛋白酶，参与哺乳动物胃中食物的消化。连续和长期使用治疗剂将导致药物与胃蛋白酶长期接触，结果，酶的结构和功能可能会改变。在这方面，通过荧光光谱法，FTIR，分子对接和分子动力学模拟等方法研究了异烟肼和利福平作为胃蛋白酶与结核病一线治疗的相互作用。根据本研究的结果，上述药物可与胃蛋白酶形成稳定的复合物，蛋白质的结构也会发生轻微变化。根据结果​​，蛋白质-药物复合物形成的主要作用力分别是异烟肼和利福平的静电力和疏水力，异烟肼显示出与蛋白质形成更强的结合力。蛋白质的FTIR光谱表明在药物存在下胃蛋白酶的结构几乎没有变化。异烟肼和利福平与胃蛋白酶结合的分子模拟结果证实了实验室结果，并表明药物的结合位点接近酶的活性位点。同样，在两种药物存在下胃蛋白酶的活性也显着增加。异烟肼和利福平与胃蛋白酶结合的分子模拟结果证实了实验室结果，并表明药物的结合位点接近酶的活性位点。同样，在两种药物存在下胃蛋白酶的活性也显着增加。异烟肼和利福平与胃蛋白酶结合的分子模拟结果证实了实验室结果，并表明药物的结合位点接近酶的活性位点。同样，在两种药物存在下胃蛋白酶的活性也显着增加。