中文摘要：

表达纯化了野生型（WT）及F185K突变型HIV-1整合酶核心区蛋白（INc），并对二者的溶解性和活性进行了比较．实验结果表明：F185K突变后INc溶解性显著提高，活性有一定程度降低．对WT和F185KIN。体系进行了1800ps的分子动力学模拟．模拟结果表明：F185KINc功能loop区柔性和蛋白质整体运动性降低，使蛋白质活性降低，F185K突变后盐桥网络的变化驱动了斟，局部构象改变，引起INc表面的部分疏水残基被包埋，亲水残基暴露，相对亲水溶剂可接近面积增大，同时，突变后Ⅳ。与水之间形成氢键的数量增加，与水之间作用加强，以上变化使INc溶解性提高．分子动力学模拟与实验结果相吻合．为理解蛋白质溶解性和对蛋白质进行可溶性改造提供了一定的理论依据．

英文摘要：

Wild type （WT） and F185K mutant type ofHIV-1 integrase catalytic domain （INc） were expressed and purified, and their solubility and activity were compared. The experiment results show that the solubility of F185K mutated INc was dramatically increased, whereas the activity was reduced to some extent. Subsequently, 1 800 ps molecular dynamics （MD） simulations for the WT and F185K type of INc in water were performed. The MD simulation results demonstrate that the flexibility of the catalytic loop region and the total mobility of F185K INc was reduced, which causes the decrease of activity. After the F185K mutation, changes of the salt bridge network drove the conformational change of INc, resulted in the burying of some hydrophobic residues and exposure of some other hydrophilic residues on the protein surface. Therefore, the relative hydrophilic solvent accessible surface of INc was increased. Moreover, the F185K mutation increased the hydrogen number between the INc protein and water molecule, as a consequence, the protein-water interaction was enhanced. These above changes contribute to the solubility increase of INc. It is found that the results obtained from MD simulation are in good agreement with the experiment data. The above mentioned results provides valuable insight for the understanding of protein solubility and will be helpful in protein engineering for increasing the solubility of proteins.