人类朊蛋白的动力学稳定性研究（英文）

Study on the dynamics stability of human prion protein

朊蛋白病是一种能在人类或者动物之间传播的致命的神经退行性疾病.尤其是人类朊蛋白疾病在近几年蔓延迅速,已经威胁到人类的健康.在本文中,我们使用分子动力学(MD)和流体分子动力学(FMD)模拟相结合的方法研究了人类朊蛋白(hPrPc)的动力学稳定性.我们通过FMD模拟产生了两个典型的hPrPc的变性结构,并进一步研究了在自然状态下这两个变性结构重折叠的过程,从关键残基、二级结构、残基-残基相互作用图等方面详细讨论了hPrPc的解折叠和重折叠路径.研究发现hPrPc的三个α-螺旋结构组成了一个疏水核心,在蛋白质的解折叠和重折叠过程中发挥了重要的作用.刚性的疏水核心就像是脚手架一般为hPrPc的重折叠提供便利.在重折叠过程中,π-螺旋和310螺旋出现几率较高,并且β-折叠的延长也更多地出现在完全解折叠的hPrPc体系中.

Prion diseases are fatal and infectious neurodegenerative diseases affecting humans and animals.Especially human prion diseases have threaten human health and become more widespread in the past few years.The dynamics stability of human prion protein（hPrPc）was studied by the molecular dynamics（MD）and flow MD（FMD）simulations.Two symbol denatured states of hPrPc were produced by the FMD simulation for the following refolding process.The unfolding and refolding paths were carefully discussed with the residues,secondary structures,and residue-residue contact map.The threeα-helices of hPrPc were assembled to form a hydrophobic core,which played key roles on the unfolding and refolding of protein.The rigid helix-core worked as a scaffold to facilitate the refolding of hPrPc.Theπ-helix and 310-helix were appeared in the refolding process.And the extending ofβ-sheet was more readily to occur in the complete unfolding system of hPrPc.