Polarization of Intraprotein Hydrogen Bond Is Critical to Thermal Stability of Short Helix
Polarization of Intraprotein Hydrogen Bond Is Critical to Thermal Stability of Short Helix
复制标题
蛋白质内氢键的极化对于短螺旋的热稳定性至关重要
DOI：
10.1021/jp208953x
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发表时间：
2012-01-12
影响因子：
3.3
通讯作者：
Mei, Ye
中科院分区：
文献类型：
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作者：
Gao, Ya;Lu, Xiaoliang;Mei, Ye
蛋白质折叠/去折叠的模拟结果在很大程度上依赖于所采用力场的准确性。即使是最简单的蛋白质结构，如短螺旋，使用现有的力场模拟往往无法产生正确的结构/热力学性质的蛋白质。最近的研究表明，缺乏极化至少是部分负责失败的成功折叠短螺旋。在这项工作中，我们开发了一个简单的公式为基础的原子电荷极化模型的蛋白质内（骨干）氢键的基础上，现有的琥珀色力场研究的热稳定性的短螺旋（2 I9 M）的复制交换分子动力学模拟。通过与标准AMBER 03力场的模拟结果比较，基于公式的原子电荷极化模型给出的螺旋熔化曲线与NMR实验结果吻合较好。然而，在使用标准琥珀力场的模拟中，螺旋在NMR实验的温度下是热不稳定的，其熔化温度几乎低于凝固点。从这两个模拟中观察到的热稳定性的差异是主链蛋白质内极化的影响，其包括在基于公式的原子电荷极化模型中。因此，骨架氢键的极化在螺旋或更一般的蛋白质结构的热稳定性中起着关键作用。
Simulation result for protein folding/unfolding is highly dependent on the accuracy of the force field employed. Even for the simplest structure of protein such as a short helix, simulations using the existing force fields often fail to produce the correct structural/thermodynamic properties of the protein. Recent research indicated that lack of polarization is at least partially responsible for the failure to successfully fold a short helix. In this work, we develop a simple formula-based atomic charge polarization model for intraprotein (backbone) hydrogen bonding based on the existing AMBER force field to study the thermal stability of a short helix (2I9M) by replica exchange molecular dynamics simulation. By comparison of the simulation results with those obtained by employing the standard AMBER03 force field, the formula-based atomic charge polarization model gave the helix melting curve in close agreement with the NMR experiment. However, in simulations using the standard AMBER force field, the helix was thermally unstable at the temperature of the NMR experiment, with a melting temperature almost below the freezing point. The difference in observed thermal stability from these two simulations is the effect of backbone intraprotein polarization, which was included in the formula-based atomic charge polarization model. The polarization of backbone hydrogen bonding thus plays a critical role in the thermal stability of helix or more general protein structures.