Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, United States of America.
PLoS One. 2013 Aug 7;8(8):e70705. doi: 10.1371/journal.pone.0070705. eCollection 2013.
Homology models of the E. coli and T. maritima chemotaxis protein CheW were constructed to assess the quality of structural predictions and their applicability in chemotaxis research: i) a model of E. coli CheW was constructed using the T. maritima CheW NMR structure as a template, and ii) a model of T. maritima CheW was constructed using the E. coli CheW NMR structure as a template. The conformational space accessible to the homology models and to the NMR structures was investigated using molecular dynamics and Monte Carlo simulations. The results show that even though static homology models of CheW may be partially structurally different from their corresponding experimentally determined structures, the conformational space they can access through their dynamic variations can be similar, for specific regions of the protein, to that of the experimental NMR structures. When CheW homology models are allowed to explore their local accessible conformational space, modeling can provide a rational path to predicting CheW interactions with the MCP and CheA proteins of the chemotaxis complex. Homology models of CheW (and potentially, of other chemotaxis proteins) should be seen as snapshots of an otherwise larger ensemble of accessible conformational space.
为了评估结构预测的质量及其在趋化研究中的适用性，构建了大肠杆菌和海洋甲烷杆菌趋化蛋白 CheW 的同源模型：i）使用海洋甲烷杆菌 CheW 的 NMR 结构作为模板构建了大肠杆菌 CheW 的模型，ii）使用大肠杆菌 CheW 的 NMR 结构作为模板构建了海洋甲烷杆菌 CheW 的模型。使用分子动力学和蒙特卡罗模拟研究了同源模型和 NMR 结构可及的构象空间。结果表明，尽管 CheW 的静态同源模型可能在结构上与相应的实验确定结构部分不同，但它们通过动态变化可及的构象空间在蛋白质的特定区域可能与实验 NMR 结构相似。当 CheW 同源模型被允许探索其局部可及构象空间时，建模可以为预测 CheW 与趋化复合物中的 MCP 和 CheA 蛋白的相互作用提供合理的途径。CheW 的同源模型（以及可能的其他趋化蛋白）应被视为更大的可及构象空间的一部分。
