钙调蛋白构象变化路径

Conformational transition pathway of calmodulin

根据已发现的钙调蛋白(CaM)打开和闭合两种不同的构象,研究了拮抗剂对构象变化的影响以及CaM全局构象变化路径.首先,进行了含拮抗剂和不含拮抗剂的两种常规分子动力学模拟,结果表明:CaM在独立存在时具有从闭合状态开启的趋势,它的构象动态变化推动了CaM变构功能的实现;拮抗剂具有将CaM的构象变化"锁住"在闭合状态的功能,有利于CaM控制一些激酶和磷酸酶的活性.在此基础上,进一步用靶向分子动力学模拟了CaM从闭合到打开的构象变化过程,得到一条稳定的变化路径和4个可能的过渡态构象.

The effects of antagonist on the conformational transition and global conformational transition pathway of calmodulin （CAM） are investigated by means of two different conformations of open and closed states. The molecular dynamics method is firstly used to simulate conformational transitions of the ealmodulins with and without an antagonist bound. The results show that CaM without antagonist tends to open from its closed state and cause allosteric interaction. And CaM with antagonist tends to keep in closed state, which is conducive to control the activities of some kinases and phosphatases. A global conformational transition between open and closed states is simulated by using targeted molecular dynamics （TMD）, and a conformational transition pathway and four possible intermediate states are obtained.