Simulated and NMR-derived backbone dynamics of a protein with significant flexibility: a comparison of spectral densities for the betaARK1 PH domain.
Simulated and NMR-derived backbone dynamics of a protein with significant flexibility: a comparison of spectral densities for the betaARK1 PH domain.
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具有显着灵活性的蛋白质的模拟和 NMR 衍生的主链动力学：betaARK1 PH 结构域的光谱密度比较。
DOI：
10.1021/ja0031117
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发表时间：
2001
影响因子：
15
通讯作者：
Cowburn,D
中科院分区：
文献类型：
--
作者：
Pfeiffer,S;Fushman,D;Cowburn,D
计算了300 K下β ARK 1 PH结构域在含有适当离子的显式水溶液中的分子动力学轨道，轨道时间为7.6 ns.在ω = 0、ω N和0.87 ω处的谱密度。考虑到蛋白质的各向异性整体运动，从实验和模拟数据评估无模型参数。实验和模拟的光谱密度是在合理的一般协议NH键矢量，相应的运动收敛在模拟时间内。一个足够的采样的NH键内的蛋白质的灵活部分的运动需要更长的模拟时间。模拟得到的谱密度J（0）和J（ω N）平均比实验值低4.5%和16%，岩心剩余物的相应数值约为6%，高频谱密度J（0.87 ω H）平均比实验值低16%（岩心为21%）。模拟的顺序参数，S2，也较低，虽然模拟和实验之间的总体分歧不太明显：1%的所有残基和6%的核心。所观察到的模拟谱密度和序参数的系统性降低与实验数据相比，可以部分归因于NH键相对于它们的肽平面的超快自由运动，这是详细分析的。这种系统差异在J（0.87 ω H）时最为明显，它似乎对内部运动的慢的、亚纳秒的时间尺度最为敏感，而J（0）和J（ω N）则由蛋白质的整体旋转翻滚所支配。实验测得的15N弛豫参数（R1，R2，NOE）和它们的值从模拟的谱密度之间观察到类似的差异。谱密度的分析提供了关于模拟数据和实验数据的比较的额外信息，这是无模型分析所不能提供的。
A 7.6 ns molecular dynamics trajectory of the βARK1 PH domain in explicit water with appropriate ions was calculated at 300 K. Spectral densities at ω = 0, ωN, and 0.87ωHand the model-free parameters were evaluated from the experimental as well as the simulated data, taking the anisotropic overall motion of the protein into account. Experimental and simulated spectral densities are in reasonable general agreement for NH bond vectors, where the corresponding motions have converged within the simulation time. A sufficient sampling of the motions for NH bonds within flexible parts of the protein requires a longer simulation time. The simulated spectral densitiesJ(0) andJ(ωN) are, on average, 4.5% and 16% lower than the experimental data; the corresponding numbers for the core residues are about 6%; the high-frequency spectral densitiesJ(0.87ωH) are lower by, on average, 16% (21% for the core). The simulated order parameters,S2, are also lower, although the overall disagreement between the simulation and experiment is less pronounced: 1% for all residues and 6% for the core. The observed systematic decrease of simulated spectral density and the order parameters compared to the experimental data can be partially attributed to the ultrafast librational motion of the NH bonds with respect to their peptide plane, which was analyzed in detail. This systematic difference is most pronounced forJ(0.87ωH), which appears to be most sensitive to the slow, subnanosecond time scale of internal motion, whereasJ(0) andJ(ωN) are dominated by the overall rotational tumbling of the protein. Similar discrepancies are observed between the experimentally measured15N relaxation parameters (R1,R2, NOE) and their values calculated from the simulated spectral densities. The analysis of spectral densities provides additional information regarding the comparison of the simulated and experimental data, not available from the model-free analysis.