Hsp70核苷酸结合域突变体影响酶活的分子动力学模拟研究

分子伴侣蛋白Hsp70氮端核苷酸结合域（NBD, nucleotide-binding domain）的ATP酶活性变化对其行使分子伴侣功能具有重要作用。本文采用分子动力学模拟方法研究酵母分子伴侣Hsp70氮端NBD内残基A17，R23，G32和R167点突变对其ATP酶活性区域构象影响及功能关系。结果表明，突变体A17V，T23H，G32S的ATP结合口袋袋口的loopl（第一个转角，连接p1与p2）结构柔性增强，活性残基T11侧链明显向内移动，从而更加接近ATP的γ-磷酸基团，更容易使ATP水解。这可能蕞终导致ATP酶活性增强，从而引起分子伴侣功能的变化。

Molecular dynamics simulation for the effect of ATP enzyme activity of Hsp70 NBD mutations

The molecular chaperone Hsp70 N-terminal NBD （nucleotide-binding domain） ATP enzyme activity plays a significant role in its molecular chaperone function. In this study, we performed molecular dynamics （MD） simulation to investigate the connection of molecular chaperone function and conformation change in Hsp70 N-terminal NBD ATP enzyme activity domain after point mutation in A17, R23, G32 and R167. Our data indicates that the point mutations, A17V, R23H and G32S enhanced the flexibility of loopl, loopl （at the first corner of NBD structure, combine 131 with 132） , which is located at the arch structure in ATP binding pocket. The side chain of T11 moved closer to the ATP γ-Pi, which is easy to hydrolyse ATP. These structural alterations might enhance the ATP enzyme activity and change the molecular chaperone function.