分子动力学模拟揭示MTHFR的温度耐受性机制

Molecular Dynamics Simulation Reveals the Mechanism of Temperature Tolerance of Methylenetetrahydrofolate Reductase

为了研究亚甲基四氢叶酸还原酶(MTHFR)的温度耐受性,我们采用分子动力学模拟的方法,构建了四种模拟体系(37、45、55和65℃)并对MTHFR分别进行了100ns的计算,分析了酶活性中心的差异及其引起的构象变化。研究发现,在37和45℃条件下,MTHFR整体构象比较稳定;大于55℃时,蛋白的三维结构可能丧失柔性,这表明蛋白质可能已达到熔解温度,通过构象分析发现高温会破坏FAD结合位点微环境。本研究在原子水平揭示了MTHFR的温度耐受等关键信息。

In order to study the temperature tolerance of methylenetetrahydrofolate reductase(MTHFR),four simulation systems(37℃,45℃,55℃and 65℃)were constructed by molecular dynamics simulation,and the MTHFR was calculated for 100 ns,respectively.The differences of enzyme active centers and the conformational changes were analyzed.It was found that the overall conformation of MTHFR was stable at 37℃and 45℃;when the temperature was higher than 55℃,the three-dimensional structure of the protein might lose its flexibility,which indicated that the protein might have reached the melting temperature.Through conformational analysis,we found that high temperature would destroy the microenvironment of FAD binding sites.This study reveals the key information of temperature tolerance of MTHFR at the atomic level.