人类朊蛋白稳定性的流体分子动力学研究（英文）

Flow Molecular Dynamics Study on the Stability of Human Prion Protein

朊蛋白病,被称为传染性海绵状脑病(TSE),或者致死性神经退行传染病,在人和动物中发病,与α-螺旋构型部分向β-折叠构型转变有关.本文使用分子动力学模拟和流体分子动力学模拟相结合的方法对野生型人类朊蛋白和R200K突变型人类朊蛋白的结构稳定性进行了研究.研究发现,α-螺旋柱交叉形成的防护墙是维持朊蛋白结构稳定的关键因素,而β-折叠活性较高.流体动力干扰在一定程度上可以不改变折叠路径并能够有效加速蛋白质的解折叠过程.

Prion diseases, known as transmissible spongiform encephalopathies （TSE）, or fatal and infections neurodegenerative diseases affecting humans and animals which are related with the structure transition of a-helix intoff sheet. In this work, wild-type human prion protein （bPrPc） and one of its mutation system m-hPrPc （R220K） were selected to study the stability of prion protein （PrPc）. The chemical and thermodynamic stability of hPrPc were investigated with the combined method of molecular dynamics （MD） and flow molecular dynamics （FMD） simulation. It was found that the protection wall composed with crossed a-helix column was the key stability factor of PrPc and/3- sheet was quite active during all the simulations. Hydrodynamic disturbance was shown to be an effective technique to accelerate the unfolding of protein without changing the unfolding pathway in some extent.