Ab initio phasing of high-symmetry macromolecular complexes:: Successful phasing of authentic poliovirus data to 3.0 Å resolution
Ab initio phasing of high-symmetry macromolecular complexes:: Successful phasing of authentic poliovirus data to 3.0 Å resolution
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DOI：
10.1006/jmbi.2001.4485
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发表时间：
2001-03-23
影响因子：
5.6
通讯作者：
Filman, DJ
中科院分区：
文献类型：
--
作者：
Miller, ST;Hogle, JM;Filman, DJ
一种基于遗传算法的计算方法，从对称的大分子结构，如二十面体病毒的晶体的衍射数据的从头算定相，已实施和应用于脊髓灰质炎病毒的P1/Mahoney株的真实数据。仅使用单波长原生衍射数据，该方法被证明能够产生正确的相位，从而电子密度，3.0埃的分辨率。在没有预先知道病毒的形状并且仅知道其大小的情况下，该方法使用遗传算法来确定服从已知的非晶体对称性（NCS）约束的病毒的粗糙的、低分辨率（这里为20.5埃）模型。这些模型的最佳评分经过细化和NCS平均，随后相位扩展到高分辨率（3.0埃）。通过测量并包括变换中的所有低分辨率项，克服了相位扩展中的初始困难。在包括低分辨率数据的情况下，该方法在由遗传算法识别的不同模型的十次试验中的每一次中成功地产生基本上正确的相位和电子密度到6.0埃。回顾性分析表明，这些正确的高分辨率解决方案收敛于一系列显著不同的低分辨率相位集（平均差异为59.7度，低于24埃）。这种方法是一种有效的方法来确定二十面体病毒的阶段，并具有生产阶段的优势，从模型的偏见。预计该方法可以推广到其他具有高NCS的蛋白质系统。(C)北京：科学出版社.
A genetic algorithm-based computational method for the nb initio phasing of diffraction data from crystals of symmetric macromolecular structures, such as icosahedral viruses, has been implemented and applied to authentic data from the P1/Mahoney strain of poliovirus. Using only single-wavelength native diffraction data, the method is shown to be able to generate correct phases, and thus electron density, to 3.0 Angstrom resolution. Beginning with no advance knowledge of the shape of the virus and only approximate knowledge of its size, the method uses a genetic algorithm to determine coarse, low-resolution (here, 20.5 Angstrom) models of the virus that obey the known non-crystallographic symmetry (NCS) constraints. The best scoring of these models are subjected to refinement and NCS-averaging, with subsequent phase extension to high resolution (3.0 Angstrom). Initial difficulties in phase extension were overcome by measuring and including all low-resolution terms in the transform. With the low-resolution data included, the method was successful in generating essentially correct phases and electron density to 6.0 Angstrom in every one of ten trials from different models identified by the genetic algorithm. Retrospective analysis revealed that these correct high-resolution solutions converged from a range of significantly different low-resolution phase sets (average differences of 59.7 degrees below 24 Angstrom). This method represents an efficient way to determine phases for icosahedral viruses, and has the advantage of producing phases free from model bias. It is expected that the method can be extended to other protein systems with high NCS. (C) 2001 Academic Press.