CAJ | 학술논문

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合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.
근거이발현적개조단백(CaM)타개화폐합량충불동적구상,연구료길항제대구상변화적영향이급CaM전국구상변화로경.수선,진행료함길항제화불합길항제적량충상규분자동역학모의,결과표명:CaM재독립존재시구유종폐합상태개계적추세,타적구상동태변화추동료CaM변구공능적실현;길항제구유장CaM적구상변화"쇄주"재폐합상태적공능,유리우CaM공제일사격매화린산매적활성.재차기출상,진일보용파향분자동역학모의료CaM종폐합도타개적구상변화과정,득도일조은정적변화로경화4개가능적과도태구상.
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 calmodulins 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.