三种金属硫蛋白动力学稳定性的理论研究

Theoretic Studies of Dynamics Stability to Three Kinds of Metallothioneins

对三类金属硫蛋白 (大鼠金属硫蛋白亚型II,兔肝金属硫蛋白亚型I和兔肝金属硫蛋白亚型II)的单体和二聚体进行了水溶液条件下的分子动力学模拟.其中大鼠金属硫蛋白亚型II的结构直接来自于晶体数据 ,兔肝金属硫蛋白亚型I和II的结构则通过同源蛋白模型搭建.动力学模拟的结果显示,这三种单体在水溶液中都具有相当大的柔性 ,柔性主要来源于柔性区的氨基酸残基.三类金属硫蛋白单体的动力学模拟均表明α结构域的动力学稳定性都要优于 β结构域.从主链的坐标均方根偏差可以看到,二聚体的动力学稳定性要明显优于单体 ,这主要因为在形成二聚体后柔性区域残基的构象空间受到了一定的限制.

Molecular dynamics calculations were performed to monomers and dimers of three kinds of metallothioneins in water solution. For these kinds of metallothioneins,the structure of MT-II in rat liver obtained directly from Protein Data Bank, while other two structures of MT-I and MT-II in rabbit liver were constructed by homology modeling. The results of molecular dynamics showed that these three kinds of MTs possessed relatively high flexibility,which mainly derived from two residues in flexible region. To three kinds of monomer, the calculations results confirmed the view that the dynamics stability ofαdomain was better than that of βdomain. Comparing the coordinates r.m.s, it could be found that the dimers are more stable than the monomers. The main reason is that the conformational space of these residues in the flexible region would be restricted to some extent when the dimers formed.