Pellegrini-Calace Marialuisa, Maiwald Tim, Thornton Janet M
EMBL/EBI, The Wellcome Trust Genome Campus, Cambridge, United Kingdom.
PLoS Comput Biol. 2009 Jul;5(7):e1000440. doi: 10.1371/journal.pcbi.1000440. Epub 2009 Jul 17.
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/.
跨膜通道蛋白通过介导离子和分子跨生物膜运输，在维持细胞的内稳态、反应性以及跨膜电化学梯度方面发挥着关键作用。因此，给定一组三维坐标后能够自动识别并描述跨膜蛋白中通道的计算方法，是深入了解其功能的关键工具。在此，我们介绍PoreWalker，一种全自动方法，它能从三维结构中检测并全面表征跨膜蛋白中的通道。该方法遵循一个逐步的过程，首先使用几何标准识别并优化孔中心和孔轴，然后检测穿过通道的最大且最长的腔。最后，计算孔的特征，包括直径轮廓、孔壁残基、孔的大小、形状和规则性，从而对通道进行定量和可视化表征。为说明该工具的用途，此方法应用于多个跨膜通道蛋白结构，并能够识别代表特定通道家族的形状/大小/残基特征。该软件可通过网络资源获取，网址为http://www.ebi.ac.uk/thornton-srv/software/PoreWalker/ 。
