Angyán Annamária F, Szappanos Balázs, Perczel András, Gáspári Zoltán
Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary.
BMC Struct Biol. 2010 Oct 29;10:39. doi: 10.1186/1472-6807-10-39.
In conjunction with the recognition of the functional role of internal dynamics of proteins at various timescales, there is an emerging use of dynamic structural ensembles instead of individual conformers. These ensembles are usually substantially more diverse than conventional NMR ensembles and eliminate the expectation that a single conformer should fulfill all NMR parameters originating from 10(16) - 10(17) molecules in the sample tube. Thus, the accuracy of dynamic conformational ensembles should be evaluated differently to that of single conformers.
We constructed the web application CoNSEnsX (Consistency of NMR-derived Structural Ensembles with eXperimental data) allowing fast, simple and convenient assessment of the correspondence of the ensemble as a whole with diverse independent NMR parameters available. We have chosen different ensembles of three proteins, human ubiquitin, a small protease inhibitor and a disordered subunit of cGMP phosphodiesterase 5/6 for detailed evaluation and demonstration of the capabilities of the CoNSEnsX approach.
Our results present a new conceptual method for the evaluation of dynamic conformational ensembles resulting from NMR structure determination. The designed CoNSEnsX approach gives a complete evaluation of these ensembles and is freely available as a web service at http://consensx.chem.elte.hu.
随着人们认识到蛋白质内部动力学在不同时间尺度上的功能作用，动态结构集合体正逐渐取代单个构象异构体被广泛使用。这些集合体通常比传统的核磁共振（NMR）集合体具有更多样性，并且消除了认为单个构象异构体应满足来自样品管中10¹⁶ - 10¹⁷个分子的所有NMR参数的期望。因此，动态构象集合体的准确性评估方式应与单个构象异构体不同。
我们构建了网络应用程序CoNSEnsX（NMR衍生结构集合体与实验数据的一致性），可快速、简单且方便地评估整个集合体与可用的各种独立NMR参数的对应关系。我们选择了三种蛋白质（人泛素、一种小蛋白酶抑制剂和cGMP磷酸二酯酶5/6的无序亚基）的不同集合体进行详细评估，并展示CoNSEnsX方法的能力。
我们的结果提出了一种用于评估由NMR结构测定产生的动态构象集合体的新概念方法。所设计的CoNSEnsX方法对这些集合体进行了全面评估，并且可作为网络服务在http://consensx.chem.elte.hu免费获取。
