The expanded FindCore method for identification of a core atom set for assessment of protein structure prediction
The expanded FindCore method for identification of a core atom set for assessment of protein structure prediction
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DOI：
10.1002/prot.24490
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发表时间：
2014-02-01
影响因子：
2.9
通讯作者：
Montelione, Gaetano T.
中科院分区：
文献类型：
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作者：
Snyder, David A.;Grullon, Jennifer;Montelione, Gaetano T.
要最大限度地发挥基于NMR的结构测定的科学影响，需要稳健且统计学上合理的方法来评估NMR衍生结构的精度。特别是，定义用于计算叠加和验证结构预测的核心原子集的方法对于使用NMR衍生结构作为CASP竞赛中的目标至关重要。FindCore（Snyder和Montelione，Proteins 2005;59：673-686）是用于鉴定核心原子集合并将该集合划分为结构域的不依赖叠加的方法。然而，由于FindCore通过敏感地排除未明确定义的原子来优化叠加，因此FindCore核心可能不包含适用于NMR结构的某些应用（包括CASP评估过程）的所有原子。调整FindCore方法来评估预测模型对CASP 10中的实验NMR结构需要修改FindCore方法。本文介绍了公约和标准协议，以计算一个“扩展FindCore”原子集，适用于生物和生物物理背景下的验证和应用。Expanded FindCore方法的一个关键应用是在实验NMR结构中识别一组核心原子，从而验证预测的蛋白质结构模型。我们展示了这种扩展的FindCore方法在表征18个NMR衍生的CASP 10目标结构的明确区域中的应用。扩展的FindCore协议定义了“扩展的核心原子集”，这些原子集与专家的直觉相匹配，即结构的哪些部分被充分定义以用于评估CASP模型预测。我们还说明了这种分析对CASP GDT评估分数的影响。Proteins 2014; 82（Suppl 2）：219-230.© 2013 Wiley Periodicals，Inc.
Maximizing the scientific impact of NMR‐based structure determination requires robust and statistically sound methods for assessing the precision of NMR‐derived structures. In particular, a method to define a core atom set for calculating superimpositions and validating structure predictions is critical to the use of NMR‐derived structures as targets in the CASP competition. FindCore (Snyder and Montelione, Proteins 2005;59:673–686) is a superimposition independent method for identifying a core atom set and partitioning that set into domains. However, as FindCore optimizes superimposition by sensitively excluding not‐well‐defined atoms, the FindCore core may not comprise all atoms suitable for use in certain applications of NMR structures, including the CASP assessment process. Adapting the FindCore approach to assess predicted models against experimental NMR structures in CASP10 required modification of the FindCore method. This paper describes conventions and a standard protocol to calculate an “Expanded FindCore” atom set suitable for validation and application in biological and biophysical contexts. A key application of the Expanded FindCore method is to identify a core set of atoms in the experimental NMR structure for which it makes sense to validate predicted protein structure models. We demonstrate the application of this Expanded FindCore method in characterizing well‐defined regions of 18 NMR‐derived CASP10 target structures. The Expanded FindCore protocol defines “expanded core atom sets” that match an expert's intuition of which parts of the structure are sufficiently well defined to use in assessing CASP model predictions. We also illustrate the impact of this analysis on the CASP GDT assessment scores. Proteins 2014; 82(Suppl 2):219–230. © 2013 Wiley Periodicals, Inc.