用分子动力学方法对Cystatin蛋白的研究

Molecular dynamics simulation of Cystatin protein

通过动力学模拟研究野生型和I66Q突变型cC的动力学特性,为设计和筛选治疗Cystatin C引起的脑淀粉样血管病药物提供重要的理论依据。通过分子动力学模拟的方法,选择可引起脑淀粉样血管病的Cystatin蛋白为模型,探讨了在形成致病状纤维过程中起到关键作用的蛋白质结构位点。研究分子动力学模拟显示,突变型cC较野生型更易形成淀粉样纤维,突变型蛋白的L1部位较野生型具有更高的柔性,更易通过结构域交换形成二聚体进而引发淀粉样纤维沉淀。该研究结果对于设计治疗相关疾病如疯牛病等的药物也有一定的借鉴意义。

To find a proper method to design and screen drugs for curing the amyloid angiopathy caused by Cystatin C, we studied the dynamics properties of wild type （WT） and I66Q mutant of chicken Cystatin （cC） by molecular dynamic simulation. By using structural model of WT cC as a starting model, we investigated WT and I66Q mutant of cC by molecular dynamics simulations to search regions critical for amyloid fibrils formation. Our results indicate that I66Q has more propensity of forming amyloid fiber than WT and its Loopl region is more flexible than WT. Thus I66Q mutant can aggregate more easily through domain swapping than WT. The properties of amyloidogenic protein can be changed by point mutation. Our results are also meaningful for designing drugs against related diseases such as BSE and so on.