PoreWalker: a novel tool for the identification and characterization of channels in transmembrane proteins from their three-dimensional structure.
PoreWalker: a novel tool for the identification and characterization of channels in transmembrane proteins from their three-dimensional structure.
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DOI：
10.1371/journal.pcbi.1000440
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发表时间：
2009-07
影响因子：
4.3
通讯作者：
Thornton JM
中科院分区：
文献类型：
--
作者：
Pellegrini-Calace M;Maiwald T;Thornton JM
跨膜通道蛋白通过介导离子和分子通过生物膜的转运，在维持细胞的稳态和响应性以及跨膜电化学梯度中起关键作用。因此，给定一组3D坐标的计算方法可以自动识别和描述跨膜蛋白中的通道，这是了解它们如何发挥作用的关键工具。在这里，我们提出了PoreWalker，一种全自动化的方法，它检测和完全表征跨膜蛋白的通道，从它们的3D结构。一个逐步的程序，其中的孔中心和孔轴首先确定和优化使用几何标准，然后通过通道的最大和最长的空腔被检测。最后，孔隙特征，包括直径分布，孔隙内衬残留物，大小，形状和规则性的孔计算，提供了一个定量和可视化的表征通道。为了说明这种工具的使用，该方法被应用到跨膜通道蛋白的几种结构，并能够识别特定通道家族的形状/大小/残基特征。该软件可在http://www.ebi.ac.uk/thornton-srv/software/PoreWalker/上作为基于网络的资源获得。跨膜通道蛋白负责离子和分子通过生物膜的运输，并且对于细胞的生理学是关键的。事实上，它们的不正确功能涉及或与几种疾病有关（糖尿病，肌强直，帕金森病等）。此外，它们对不同离子或分子的特异性和选择性已被假设，有时显示强烈依赖于通道的形状和大小或氨基酸组成。因此，计算方法来识别和定量跨膜蛋白结构中的跨膜通道几何形状是更好地理解它们如何发挥功能的关键工具。我们已经开发了PoreWalker，一种新的方法来检测和描述这些通道的几何形状在跨膜蛋白从他们的三维结构。该方法是完全自动化的，非常用户友好的，确定的通道的位置，并得出了一些通道的功能：在给定的高度沿着通道的直径分布，所有的残留物内衬通道壁，大小，形状和规则的通道。这些特征对于研究这些通道如何发挥作用非常有帮助。我们已经将PoreWalker应用于几种通道蛋白结构，并能够识别代表特定通道家族的形状/大小/残基特征。
Transmembrane channel proteins play pivotal roles in maintaining the homeostasis and responsiveness of cells and the cross-membrane electrochemical gradient by mediating the transport of ions and molecules through biological membranes. Therefore, computational methods which, given a set of 3D coordinates, can automatically identify and describe channels in transmembrane proteins are key tools to provide insights into how they function. Herein we present PoreWalker, a fully automated method, which detects and fully characterises channels in transmembrane proteins from their 3D structures. A stepwise procedure is followed in which the pore centre and pore axis are first identified and optimised using geometric criteria, and then the biggest and longest cavity through the channel is detected. Finally, pore features, including diameter profiles, pore-lining residues, size, shape and regularity of the pore are calculated, providing a quantitative and visual characterization of the channel. To illustrate the use of this tool, the method was applied to several structures of transmembrane channel proteins and was able to identify shape/size/residue features representative of specific channel families. The software is available as a web-based resource at http://www.ebi.ac.uk/thornton-srv/software/PoreWalker/. Transmembrane channel proteins are responsible for the transport of ions and molecules through biological membranes and are pivotal for the physiology of the cell. In fact, their incorrect functioning is involved or related to several diseases (diabetes, myotonia, Parkinson's disease, etc.). Moreover, their specificity and selectivity to different ions or molecules have been hypothesized and sometimes shown to strongly depend on the shape and size or amino acid composition of the channel. Therefore, computational methods to identify and quantitatively characterise channel geometry in transmembrane protein structures are key tools to better understand how they function. We have developed PoreWalker, a new method to detect and describe the geometry of these channels in transmembrane proteins from their 3D structures. The method is fully automated, very user-friendly, identifies the location of the channel and derives a number of channel features: diameter profiles at given heights along the channel, all the residues lining the channel walls, size, shape and regularity of the channel. These features can be very helpful in the study of how these channels might function. We have applied PoreWalker to several channel protein structures and were able to identify shape/size/residue features that were representative of specific channel families.
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影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
3.5
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MacKinnon, R
通讯作者：
MacKinnon, R
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Dutzler, Raimund