Automated evaluation of quaternary structures from protein crystals.
Automated evaluation of quaternary structures from protein crystals.
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DOI：
10.1371/journal.pcbi.1006104
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发表时间：
2018-04
影响因子：
4.3
通讯作者：
Duarte JM
中科院分区：
文献类型：
--
作者：
Bliven S;Lafita A;Parker A;Capitani G;Duarte JM
正确评估蛋白质的四级结构是了解其功能、理化性质和与其他蛋白质相互作用模式的基本前提。目前，蛋白质数据库中约90%的结构是晶体结构，其中正确的四级结构嵌入在许多晶体接触之间的晶格中。需要计算方法来1）将晶格中的所有蛋白质-蛋白质接触分类为生物相关或晶体接触，以及2）提供生物相关界面如何联合收割机成生物组装体的评估。在我们以前的工作中，我们解决了我们的EPPIC（进化蛋白质蛋白质界面分类器）方法的第一个问题。在这里，我们提出了我们的解决方案，第二个问题的一种新的方法，结合接口分类结果与对称性和拓扑结构的考虑。新算法使用晶格的图形表示来枚举晶体内所有可能的有效组件，并基于成对接口评分来预测最可能的生物单元。我们的方法在具有PDB注释共识的1，481个生物组件的新数据集上实现了85%的精确度（对于不同的寡聚体类型，范围从76%到90%）。虽然几乎相同的精度是由比萨，目前最流行的四级结构分配方法，我们表明，由于从根本上不同的方法来解决这个问题，这两种方法是互补的，可以结合起来，以提高生物组装分配。用于蛋白质组装自动评估的软件（EPPIC第3版）已通过http://www.eppic-web.org的网络服务器提供。X射线衍射实验是揭示蛋白质详细原子三维结构的主要实验技术。在这些实验中，蛋白质被包装到晶体中，这是一个远离其天然溶液环境的环境。确定结构的哪些部分反映了蛋白质在细胞中的状态，而不是晶体环境的人工制品，可能是一项艰巨的任务。不同的蛋白质亚基在溶液中如何组装在一起被称为四级结构。找到正确的四级结构对于理解蛋白质寡聚化和蛋白质-蛋白质相互作用都很重要。在这里，我们提出了一种新的方法来自动确定蛋白质的四级结构给定其晶体结构。我们提供了正确的蛋白质组装体应具备的属性的理论基础，并根据这些属性提供了所有可能的组装体的系统评估。该方法为实验结构生物学家和结构生物信息学家批量分析蛋白质结构提供了指导。蛋白质数据库中的所有蛋白质都通过一个公共网站和数据库提供组装，该网站和数据库每周更新一次，以发布新的结构。
A correct assessment of the quaternary structure of proteins is a fundamental prerequisite to understanding their function, physico-chemical properties and mode of interaction with other proteins. Currently about 90% of structures in the Protein Data Bank are crystal structures, in which the correct quaternary structure is embedded in the crystal lattice among a number of crystal contacts. Computational methods are required to 1) classify all protein-protein contacts in crystal lattices as biologically relevant or crystal contacts and 2) provide an assessment of how the biologically relevant interfaces combine into a biological assembly. In our previous work we addressed the first problem with our EPPIC (Evolutionary Protein Protein Interface Classifier) method. Here, we present our solution to the second problem with a new method that combines the interface classification results with symmetry and topology considerations. The new algorithm enumerates all possible valid assemblies within the crystal using a graph representation of the lattice and predicts the most probable biological unit based on the pairwise interface scoring. Our method achieves 85% precision (ranging from 76% to 90% for different oligomeric types) on a new dataset of 1,481 biological assemblies with consensus of PDB annotations. Although almost the same precision is achieved by PISA, currently the most popular quaternary structure assignment method, we show that, due to the fundamentally different approach to the problem, the two methods are complementary and could be combined to improve biological assembly assignments. The software for the automatic assessment of protein assemblies (EPPIC version 3) has been made available through a web server at http://www.eppic-web.org. X-ray diffraction experiments are the main experimental technique to reveal the detailed atomic 3-dimensional structure of proteins. In these experiments, proteins are packed into crystals, an environment that is far away from their native solution environment. Determining which parts of the structure reflect the protein’s state in the cell rather than being artifacts of the crystal environment can be a difficult task. How the different protein subunits assemble together in solution is known as the quaternary structure. Finding the correct quaternary structure is important both to understand protein oligomerization and for the understanding of protein-protein interactions at large. Here we present a new method to automatically determine the quaternary structure of proteins given their crystal structure. We provide a theoretical basis for properties that correct protein assemblies should possess, and provide a systematic evaluation of all possible assemblies according to these properties. The method provides a guidance to the experimental structural biologist as well as to structural bioinformaticians analyzing protein structures in bulk. Assemblies are provided for all proteins in the Protein Data Bank through a public website and database that is updated weekly as new structures are released.
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影响因子：
5.6
作者：
Myers-Turnbull D;Bliven SE;Rose PW;Aziz ZK;Youkharibache P;Bourne PE;Prlić A
通讯作者：
Prlić A
影响因子：
7.7
作者：
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影响因子：
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作者：
Korkhov, Vladimir M.;Mireku, Samantha A.;Locher, Kaspar P.
通讯作者：
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影响因子：
4.3
作者：
Levy ED;Pereira-Leal JB;Chothia C;Teichmann SA
通讯作者：
Teichmann SA
使用新的决定因素有效区分生物相关接触和晶体堆积接触
影响因子：
2.9
作者：
Luo, Jiesi;Guo, Yanzhi;Li, Menglong
通讯作者：
Li, Menglong