Bridging the information gap: Computational tools for intermediate resolution structure interpretation
Bridging the information gap: Computational tools for intermediate resolution structure interpretation
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DOI：
10.1006/jmbi.2001.4633
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发表时间：
2001-05-18
影响因子：
5.6
通讯作者：
Chiu, W
中科院分区：
文献类型：
--
作者：
Jiang, W;Baker, ML;Chiu, W
由于其体积大、性质复杂，很少有大型大分子配合物能达到原子分辨率。这导致了在已知结构和褶皱库中，这些由新颖和/或同源褶皱组成的结构的代表性不足。虽然通常很难实现这些结构的高分辨率模型，但x射线晶体学和电子低温显微镜能够在低到中等分辨率下确定大型组件的结构。为了帮助解释和分析这种结构，我们开发了两个程序：helixhunter和foldhunter。Helixhunter能够通过对三维密度图进行五维相互关联搜索，然后进行特征提取，可靠地识别螺旋的位置、方向和长度。Helixhunter的结果可以反过来用于探测从蛋白质数据库（PDB）中导出的二级结构元素库。从这一分析中，可以识别潜在的同源褶皱或根据α螺旋元素的排列提出新的褶皱，从而产生基于结构的含有α螺旋的褶皱识别。Foldhunter使用六维相互关联搜索，允许探针结构在目标结构的区域或组件内安装。因此，结构拟合提供了一种定量的方法来进一步检查大型复杂组件的结构和组织。这两种方法已经成功地用PDB模拟的结构在6到12埃的分辨率上进行了测试。通过将helixhunter和foldhunter整合到序列和结构信息学技术中，我们有可能推断或确认大型复合物中结构域或成分中的已知或新的褶皱。(C) 2001学术出版社。
Due to large sizes and complex nature, few large macromolecular complexes have been solved to atomic resolution. This has lead to an under-representation of these structures, which are composed of novel and/or homologous folds, in the library of known structures and folds. While it is often difficult to achieve a high-resolution model for these structures, X-ray crystallography and electron cryomicroscopy are capable of determining structures of large assemblies at low to intermediate resolutions. To aid in the interpretation and analysis of such structures, we have developed two programs: helixhunter and foldhunter. Helixhunter is capable of reliably identifying helix position, orientation and length using a five-dimensional cross-correlation search of a three-dimensional density map followed by feature extraction. Helixhunter's results can in turn be used to probe a library of secondary structure elements derived from the structures in the Protein Data Bank (PDB). From this analysis, it is then possible to identify potential homologous folds or suggest novel folds based on the arrangement of alpha helix elements, resulting in a structure-based recognition of folds containing alpha helices. Foldhunter uses a six-dimensional cross-correlation search allowing a probe structure to be fitted within a region or component of a target structure. The structural fitting therefore provides a quantitative means to further examine the architecture and organization of large, complex assemblies. These two methods have been successfully tested with simulated structures modeled from the PDB at resolutions between 6 and 12 Angstrom. With the integration of helixhunter and foldhunter into sequence and structural informatics techniques, we have the potential to deduce or confirm known or novel folds in domains or components within large complexes. (C) 2001 Academic Press.