应用ABEEMσπ/MM模型探讨小α-螺旋在显性水中折叠/展开的可逆过程

Reversible folding/unfolding of small α-helix in explicit solvent investigated by ABEEMσπ/MM

应用ABEEMσπ/MM模型进行分子动力学模拟,研究了显性水溶液中小α-螺旋(短肽Ala5)折叠/展开的可逆过程.动力学分析显示,300K下α-螺旋可以保存2ns的时间,该结果支持Margulis等人的结论.每个结构与α-螺旋结构骨架重原子的均方根偏差的时间轨迹指出,"300K下螺旋成核现象在0.1ns内快速发生"的结论是不恰当的.通过对300、400和500K温度下的研究,首次定量地给出各温度下螺旋保存的时间分别为2ns、1～1.5ns和0.8ns,并且增加温度并不改变折叠/展开的方式,只是改变折叠/展开的速率.本文对"转化态集合"结构的分析表明,从螺旋到卷曲的转换,主要通过螺旋端的氢键断裂发生(92%)、尤其是C端的氢键断裂发生(50%).氢键的破坏和形成在0.1ns的时间内完成.

We have performed molecular dynamics simulations on the reversible folding/unfolding of small （z-helix （short Ala based peptide Ala5） in explicit water solvent in terms of ABEEMσπ/MM. A dynamics analysis shows that the α-helical turn can be preserved up to a period of about 2 ns at 300 K, which supports the conclusions of Margulis et al. The time trajectory of the root mean square deviation between the heavy atoms of the backbone and the helical reference structure indicate that ＂helix melting and formation occurs rapidly on a time scale of 0.1 ns at 300 K＂ is not a felicitous conclusion. We first quantificationally concluded that the helix nucleation can maintain 2 ns, 1-1.5 ns and 0.8 ns for Alas at 300 K, 400 K and 500 K, respectively. Furthermore, increasing temperature dose not alter the pathway of folding/unfolding, but change the rate. An analysis of structures in a ＂transition-state ensemble＂ shows that helix-to-coil transitions occurs predominantly through breaking of hydrogen bonds at the helix ends （92%）, particularly at the C-terminus（50%）. Hydrogen bonds＇ breaking and formation occurs on a time scale of 0.1 ns.