Volume exclusion in calcium selective channels
Volume exclusion in calcium selective channels
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DOI：
10.1529/biophysj.107.122796
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发表时间：
2008-05-01
影响因子：
3.4
通讯作者：
Gillespie, Dirk
中科院分区：
文献类型：
--
作者：
Boda, Dezso;Nonner, Wolfgang;Gillespie, Dirk
另一个研究小组提出了一个有趣的钙通道选择性模型。然而，根据他们报告的结果，我们发现不可能评估他们的模型的优点，因为他们的结果和关于选择性的声明是基于外推超过四个数量级的低Ca2+浓度。他们的结果和主张已在几篇文章和几个期刊的评论中提出，因此需要引起注意。在这篇文章中，我们首先建立，我们获得的结果静电和通道占用类似的高浓度模拟。然后，我们进行巨正则系综模拟，使我们能够研究微摩尔Ca2+浓度。我们发现，他们的模型通道只有弱的钙离子选择性。他们的模型的一个关键问题似乎是将带负电荷的谷氨酸结构元件放置在蛋白质内的固定位置，而不是作为过滤器内的灵活单元。
Another research group has proposed an interesting model for calcium channel selectivity. However, on the basis of their reported results we find it impossible to assess the merits of their model because their results and claims concerning selectivity are based on an extrapolation over four orders of magnitude to low Ca2+ concentration. Their results and claims have been presented in several articles and reviews in several journals and, thus, need attention. In this article, we first establish that we obtain results on electrostatics and channel occupancies similar to the high-concentration simulations they present. We then perform grand canonical ensemble simulations that enable us to study micromolar Ca2+ concentrations. We find that their model channel is only weakly Ca2+ selective. A crucial problem with their model appears to be the placement of the negatively charged glutamate structural elements in fixed positions inside the protein rather than as flexible units inside the filter.