Calculation of NMR-relaxation parameters for flexible molecules from molecular dynamics simulations
Calculation of NMR-relaxation parameters for flexible molecules from molecular dynamics simulations
复制标题
DOI：
10.1023/a:1011241030461
复制
发表时间：
2001-08-01
影响因子：
2.7
通讯作者：
van Gunsteren, WF
中科院分区：
文献类型：
--
作者：
Peter, C;Daura, X;van Gunsteren, WF
相对小的分子，如肽，可以显示出高的内部流动性，在几个构象最小值之间的转换，有时旋转和内部自由度之间的耦合。在这些情况下，核磁共振弛豫数据的解释是困难的，使用标准方法进行结构测定是值得怀疑的。另一方面，在这些系统大小的情况下，旋转和内部运动的时间尺度是可访问的分子动力学（MD）模拟使用显式溶剂。因此，不再需要将MD轨迹上的距离平均值（（-1/6）或（1/3））与NOE（或ROE）导出的距离进行比较，完整光谱的（反向）计算变得可能。在本研究中，我们使用两个200 ns的轨迹的七肽的β-氨基酸在甲醇中在两个不同的温度下获得理论ROESY光谱通过计算的精确的谱密度的质子间矢量和完整的弛豫矩阵。然后将这些数据与实验数据进行比较。这种分析允许测试一些假设和近似，通常必须作出解释NMR光谱，并作出更可靠的预测的构象平衡，导致实验光谱。
Comparatively small molecules such as peptides can show a high internal mobility with transitions between several conformational minima and sometimes coupling between rotational and internal degrees of freedom. In those cases the interpretation of NMR relaxation data is difficult and the use of standard methods for structure determination is questionable. On the other hand, in the case of those system sizes, the timescale of both rotational and internal motions is accessible by molecular dynamics (MD) simulations using explicit solvent. Thus a comparison of distance averages ( (-1/6) or (1/3)) over the MD trajectory with NOE (or ROE) derived distances is no longer necessary, the (back)calculation of the complete spectra becomes possible. In the present study we use two 200 ns trajectories of a heptapeptide of beta -amino acids in methanol at two different temperatures to obtain theoretical ROESY spectra by calculating the exact spectral densities for the interproton vectors and the full relaxation matrix. Those data are then compared with the experimental ones. This analysis permits to test some of the assumptions and approximations that generally have to be made to interpret NMR spectra, and to make a more reliable prediction of the conformational equilibrium that leads to the experimental spectrum.