Nilges Michael, Bernard Aymeric, Bardiaux Benjamin, Malliavin Thérèse, Habeck Michael, Rieping Wolfgang
Institut Pasteur, Département de Biologie Structurale et Chimie, Unité de Bio-informatique Structurale, CNRS URA 2185, 25-28 rue du docteur Roux, F-75015 Paris, France.
Structure. 2008 Sep 10;16(9):1305-12. doi: 10.1016/j.str.2008.07.008.
The use of generous distance bounds has been the hallmark of NMR structure determination. However, bounds necessitate the estimation of data quality before the calculation, reduce the information content, introduce human bias, and allow for major errors in the structures. Here, we propose a new rapid structure calculation scheme based on Bayesian analysis. The minimization of an extended energy function, including a new type of distance restraint and a term depending on the data quality, results in an estimation of the data quality in addition to coordinates. This allows for the determination of the optimal weight on the experimental information. The resulting structures are of better quality and closer to the X-ray crystal structure of the same molecule. With the new calculation approach, the analysis of discrepancies from the target distances becomes meaningful. The strategy may be useful in other applications-for example, in homology modeling.
使用宽松的距离限制一直是核磁共振结构测定的标志。然而，在计算之前，距离限制需要对数据质量进行估计，会减少信息含量，引入人为偏差，并可能导致结构出现重大误差。在此，我们提出一种基于贝叶斯分析的新型快速结构计算方案。通过最小化一个扩展能量函数，该函数包括一种新型的距离约束和一个取决于数据质量的项，除了坐标之外，还能估计数据质量。这使得能够确定实验信息的最佳权重。所得结构质量更高，且更接近同一分子的X射线晶体结构。采用这种新的计算方法，对与目标距离的差异进行分析变得有意义。该策略可能在其他应用中有用，例如在同源建模中。
