Automated combined assignment of NOESY spectra and three-dimensional protein structure determination
Automated combined assignment of NOESY spectra and three-dimensional protein structure determination
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DOI：
10.1023/a:1018383106236
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发表时间：
1997-12-01
影响因子：
2.7
通讯作者：
Wüthrich, K
中科院分区：
文献类型：
--
作者：
Mumenthaler, C;Güntert, P;Wüthrich, K
提出了一种基于迭代过程的蛋白质结构自动测定方法，在迭代过程中NOESY峰表分配和结构计算同时进行。输入包括NOESY峰位置列表和从序列特定共振分配中获得的化学位移列表。对于该方法的当前应用，前面介绍的NOAH例程在距离几何程序DIANA中实现。作为一个例子，我们分析了六种蛋白质的二维和三维NOESY交叉峰列表，其中多肽主链和氨基酸侧链具有完整的序列特异性H-1配位。自动化方法分配了所有NOESY交叉峰的70-90%，比交互方法平均少10%，并且只有0.8% - 2.4%的自动分配峰与相应的手动分配峰列表中的分配不同。NOAH/DIANA获得的结构与手工分配的峰表非常一致，两种方法的剩余约束违规都对应于高质量的核磁共振结构确定。对代表相应的自动和相互作用确定的结构的构象束的系统比较表明，两种方法都没有明显的偏差，表明从核磁共振光谱中自动确定结构迈出了重要的一步。
A procedure for automated protein structure determination is presented that is based on an iterative procedure during which the NOESY peak list assignment and the structure calculation are performed simultaneously. The input consists of a list of NOESY peak positions and a list of chemical shifts as obtained from sequence-specific resonance assignment. For the present applications of this approach the previously introduced NOAH routine was implemented in the distance geometry program DIANA. As an illustration, experimental 2D and 3D NOESY cross-peak lists of six proteins have been analyzed, for which complete sequence-specific H-1 assignments are available for the polypeptide backbone and the amino acid side chains. The automated method assigned 70-90% of all NOESY cross peaks, which is on average 10% less than with the interactive approach, and only between 0.8% and 2.4% of the automatically assigned peaks had a different assignment than in the corresponding manually assigned peak lists. The structures obtained with NOAH/DIANA are in close agreement with those from manually assigned peak lists, and with both approaches the residual constraint violations correspond to high-quality NMR structure determinations. Systematic comparisons of the bundles of conformers that represent corresponding automatically and interactively determined structures document the absence of significant bias in either approach, indicating that an important step has been made towards automation of structure determination from NMR spectra.