Docking and scoring protein complexes: CAPRI 3rd edition
Docking and scoring protein complexes: CAPRI 3rd edition
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DOI：
10.1002/prot.21804
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发表时间：
2007-12-01
影响因子：
2.9
通讯作者：
Wodak, Shoshana J.
中科院分区：
文献类型：
--
作者：
Lensink, Marc F.;Mendez, Raul;Wodak, Shoshana J.
通过评估2005-2007年期间进行的盲预测来评估在原子尺度上预测蛋白质-蛋白质相互作用的方法的性能，盲预测是预测相互作用的关键评估（卡普里）的社区范围实验的第6-12轮的一部分。这些回合还包括一个新的评分实验，其中由预测因子贡献的更大的模型集可用于开发评分函数的小组。这些小组对上传的数据集进行评分，并提交他们自己的最佳模型进行评估。包括一个同源二聚体在内的九个蛋白质复合物的结构被用作靶标。这些靶标代表涉及基因表达、信号转导、RNA或蛋白质加工和膜维持的生物学相关相互作用。对于除一个靶点之外的所有靶点，预测都是从实验确定的自由（未结合）组分的结构或从同源性推导的模型开始的，这使得对接方法必须对通常伴随着结合的构象变化进行建模。总共有63个小组和8个自动服务器提交了对接预测，比前几年有了大幅度的增加，本报告对其中1994年的情况进行了评价。15个小组提交了305个模型，用于评分实验中的5个目标。对预测的评估显示，31个不同的小组为所有的目标，除了同源二聚体，产生了可接受的和中等精度的模型，但只有一个高精度的提交。在后者中，没有一个对接程序复制正确组装所需的大的构象调整，再次强调处理蛋白质的灵活性仍然是一个重大挑战。在评分实验中，很大一部分小组达到了设定的目标，即在有限的贡献模型集合中从不正确的解决方案中挑出正确的关联模式。但总的来说，他们似乎无法确定最佳模型，这表明目前的评分方法可能不够敏感。随着人们对蛋白质组装的日益关注，特别是通过结构基因组学的努力，越来越多的卡普里预测因子比以往任何时候都更积极地参与开发更好的评分函数和建模构象灵活性的方法，这有望在未来取得更大的进展。
The performance of methods for predicting protein-protein interactions at the atomic scale is assessed by evaluating blind predictions performed during 2005-2007 as part Of Rounds 6-12 of the community-wide experiment on Critical Assessment of PRedicted Interactions (CAPRI). These Rounds also included a new scoring experiment, where a larger set of models contributed by the predictors was made available to groups developing scoring functions. These groups scored the uploaded set and submitted their own best models for assessment. The structures of nine protein complexes including one homodimer were used as targets. These targets represent biologically relevant interactions involved in gene expression, signal transduction, RNA, or protein processing and membrane maintenance. For all the targets except one, predictions started from the experimentally determined structures of the free (unbound) components or from models derived by homology, making it mandatory for docking methods to model the conformational changes that often accompany association. In total, 63 groups and eight automatic servers, a substantial increase from previous years, submitted docking predictions, of which 1994 were evaluated here. Fifteen groups submitted 305 models for five targets in the scoring experiment. Assessment of the predictions reveals that 31 different groups produced models of acceptable and medium accuracy-but only one high accuracy submission-for all the targets, except the homodimer. In the latter, none Of the docking procedures reproduced the large conformational adjustment required for correct assembly, underscoring yet again that handling protein flexibility remains a major challenge. In the scoring experiment, a large fraction of the groups attained the set goal of singling out the correct association modes from incorrect solutions in the limited ensembles of contributed models. But in general they seemed unable to identify the best models, indicating that current scoring methods are probably not sensitive enough. With the increased focus on protein assemblies, in particular by structural genomics efforts, the growing community of CAPRI predictors is engaged more actively than ever in the development of better scoring functions and means of modeling conformational flexibility, which hold promise for much progress in the future.