Abseher R, Lüdemann S, Schreiber H, Steinhauser O
Institut für Theoretische Chemie, Universität Wien, Austria.
J Mol Biol. 1995 Jun 9;249(3):604-24. doi: 10.1006/jmbi.1995.0322.
A one nanosecond molecular dynamics simulation of ubiquitin in solution has been used for the calculation of the total dipolar, the radial and the reorientational correlation functions of 174 interproton NOEs and the 76 peptide chain NH vectors. The NOEs have been classified according to the structural elements they are associated with. Using multiexponential fits of the raw data spectral densities and cross-relaxation rate constants have been determined. Statistical distributions of correlation function parameters are given. On the basis of these data the assumptions underlying the standard method for distance measurement using NOE enhancements have been scrutinized. The separability of elongation and reorientation is verified for the vast majority of NOEs, but the rigid-body assumption is not supported by the simulation results. Relying on a spectral density expression that neither makes use of the product approximation nor neglects spatially restricted motion, a "bias-free" (with regard to molecular motion) distance measurement method is suggested and compared with the standard method. Errors in distances up to 24% and 50% occur due to the neglect of the dispersion of order parameters and correlation times, respectively. The preconditions for a class-specific calibration method have been investigated. Within the framework of the product approximation a method for decomposing the total cross-relaxation rate constant into contributions from radial and angular motion has been developed and applied. In several cases distance fluctuation contributes significantly to cross-relaxation with both amplitude and time behaviour.
对溶液中泛素进行了1纳秒的分子动力学模拟，用于计算174个质子间核Overhauser效应（NOE）以及76个肽链NH向量的总偶极、径向和重取向相关函数。根据与NOE相关的结构元件对其进行了分类。通过对原始数据的多指数拟合确定了光谱密度和交叉弛豫速率常数。给出了相关函数参数的统计分布。基于这些数据，对使用NOE增强进行距离测量的标准方法所依据的假设进行了仔细审查。对于绝大多数NOE，验证了伸长和重取向的可分离性，但模拟结果不支持刚体假设。基于既不使用乘积近似也不忽略空间受限运动的光谱密度表达式，提出了一种“无偏差”（关于分子运动）的距离测量方法，并与标准方法进行了比较。由于分别忽略了序参量和相关时间的色散，距离误差分别高达24%和50%。研究了类特异性校准方法的前提条件。在乘积近似的框架内，开发并应用了一种将总交叉弛豫速率常数分解为径向和角向运动贡献的方法。在几种情况下，距离波动对交叉弛豫的幅度和时间行为都有显著贡献。
