Macromolecular docking restrained by a small angle X-ray scattering profile.
Macromolecular docking restrained by a small angle X-ray scattering profile.
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DOI：
10.1016/j.jsb.2010.09.023
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发表时间：
2011-03
影响因子：
3
通讯作者：
Sali, Andrej
中科院分区：
文献类型：
--
作者：
Schneidman-Duhovny, Dina;Hammel, Michal;Sali, Andrej
虽然单一蛋白质成分的许多结构已经可用，但其复合物的结构表征仍然具有挑战性。由于蛋白质的灵活性和不准确的评分功能，对单个组件的组装结构进行建模的方法经常会出现较大的错误。然而，当有额外的信息可用时，就有可能减少错误并计算出接近原生的复杂结构。其中一种类型的信息是小角度 X 射线散射 (SAXS) 剖面，可以以高通量方式从溶液中的少量样品中收集。在这里，我们提出了一种利用 SAXS 配置文件进行蛋白质-蛋白质对接的有效方法（FoXSDock）：通过与 PatchDock 的刚性全局对接生成复杂模型，根据 SAXS 配置文件过滤模型，对模型进行聚类，并通过与 FireDock 灵活对接来细化接口。 FoXSDock 以具有模拟 SAXS 图谱的 124 个蛋白质复合物以及具有实验确定的 SAXS 图谱的 6 个复合物为基准。当诱导拟合小于 1.5Å 界面 C⟨ RMSD 且组件结构缺失分数残差小于 3% 时，FoXSDock 可以在 77% 的情况下在前 10 个预测中找到接近原生结构的模型；相比之下，仅靠对接仅能在 34% 的情况下成功。因此，综合方法显着改善了单独的分子对接。这种改进源于刚性对接采样分辨率的提高和更准确的评分。
While many structures of single protein components are becoming available, structural characterization of their complexes remains challenging. Methods for modeling assembly structures from individual components frequently suffer from large errors, due to protein flexibility and inaccurate scoring functions. However, when additional information is available, it may be possible to reduce the errors and compute near-native complex structures. One such type of information is a small angle X-ray scattering (SAXS) profile that can be collected in a high-throughput fashion from a small amount of sample in solution. Here, we present an efficient method for protein-protein docking with a SAXS profile (FoXSDock): generation of complex models by rigid global docking with PatchDock, filtering of the models based on the SAXS profile, clustering of the models, and refining the interface by flexible docking with FireDock. FoXSDock is benchmarked on 124 protein complexes with simulated SAXS profiles, as well as on 6 complexes with experimentally determined SAXS profiles. When induced fit is less than 1.5Å interface C⟨ RMSD and the fraction residues of missing from the component structures is less than 3%, FoXSDock can find a model close to the native structure within the top 10 predictions in 77% of the cases; in comparison, docking alone succeeds in only 34% of the cases. Thus, the integrative approach significantly improves on molecular docking alone. The improvement arises from an increased resolution of rigid docking sampling and more accurate scoring.
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影响因子：
5.6
作者：
Foerster, Friedrich;Webb, Benjamin;Krukenberg, Kristin A.;Tsuruta, Hiro;Agard, David A.;Sali, Andrej
通讯作者：
Sali, Andrej
影响因子：
56.9
作者：
CONNOLLY, ML
通讯作者：
CONNOLLY, ML
DOI：
10.1016/j.bbrc.2003.08.093
发表时间：
2003-10-03
影响因子：
3.1
作者：
de Azevedo, WF;dos Santos, GC;Santos, DS
通讯作者：
Santos, DS
影响因子：
3.4
作者：
Chacón, P;Morán, F;Andreu, JM
通讯作者：
Andreu, JM
影响因子：
6.1
作者：
FRASER, RDB;MACRAE, TP;SUZUKI, E
通讯作者：
SUZUKI, E