Barstar has a highly dynamic hydrophobic core: evidence from molecular dynamics simulations and nuclear magnetic resonance relaxation data.
Barstar has a highly dynamic hydrophobic core: evidence from molecular dynamics simulations and nuclear magnetic resonance relaxation data.
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Barstar 具有高度动态的疏水核心：来自分子动力学模拟和核磁共振弛豫数据的证据。
DOI：
10.1021/bi980552i
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Daggett,V
中科院分区：
文献类型：
--
作者：
Wong,KB;Daggett,V
采用分子动力学方法研究了核糖核酸酶抑制剂barstar在显式水中的动力学行为。进行了两次2.5 ns的MD模拟，生成了25000个结构的系综。该合奏再现的解决方案的结构，并与实验结构的限制NMR光谱是一致的。通过计算自相关函数和广义S2阶参数监测主链NH键矢量和侧链甲基的重取向。在100 ps的时间尺度上的运动推导出的顺序参数进行了比较，从NMR弛豫测量得到的。与实验一致，骨架NH键载体是相对刚性的。与此相反，侧链甲基表现出广泛的动态范围，从限制运动可比的骨干快速无限制的运动。甲基基团的顺序参数与它们与主链的空间分离相关，并且是残基类型依赖的。亮氨酸甲基的S2轴值较小，部分原因是两种主要旋转异构体（g+t和tg-）之间的侧链跳跃。运动，如芳环的翻转和亮氨酸侧链的跳跃是普遍的疏水核心内，这表明该核心是流体样的天然构象substates之间的低能量障碍。因此，我们的研究表明，熵的天然状态可以是显着的，不应该被打折的热力学考虑蛋白质折叠。在我们的研究结果的基础上，侧链运动代表的原生状态和熵的考虑仅基于骨干动力学的剩余熵的主要来源将是不完整的。
The dynamic behavior of the ribonuclease inhibitor barstar has been investigated by molecular dynamics (MD) simulations in explicit water. Two 2.5 ns MD simulations were performed, and an ensemble of 25 000 structures was generated. This ensemble reproduces the solution structures and is consistent with the experimental structural restraints from NMR spectroscopy. Reorientation of the backbone NH bond vectors and side chain methyl groups was monitored by calculation of autocorrelation functions and the generalizedS2order parameters. Order parameters derived for motion in the ∼100 ps time scale were compared with those obtained from NMR relaxation measurements. Consistent with experiment, the backbone NH bond vectors were relatively rigid. In contrast, the side chain methyl groups exhibited a wide dynamic range, from restricted motion comparable to that of the backbone to rapid unrestricted motion. The order parameters for the methyl groups correlate well with their spatial separation from the backbone and are residue-type dependent. SmallerS2axisvalues were observed for leucine methyl groups, in part due to side chain hopping between two predominant rotamers (g+t and tg-). Motions such as the flipping of aromatic rings and the hopping of leucine side chains were prevalent within the hydrophobic core, suggesting that the core is fluid-like with low energy barriers between native conformational substates. Thus, our studies suggest that the entropy of the native state can be significant and should not be discounted in thermodynamic considerations of protein folding. On the basis of our results, the side chain motion represents the primary source of the residual entropy of the native state and entropic considerations based solely on backbone dynamics would be incomplete.