Finding and Characterizing Tunnels in Macromolecules with Application to Ion Channels and Pores
Finding and Characterizing Tunnels in Macromolecules with Application to Ion Channels and Pores
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DOI：
10.1529/biophysj.108.135970
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发表时间：
2009-01-21
影响因子：
3.4
通讯作者：
Sharp, Kim A.
中科院分区：
文献类型：
--
作者：
Coleman, Ryan G.;Sharp, Kim A.
我们描述了一种新的算法，CHUNNEL，自动发现，表征和显示蛋白质中的隧道或孔。在构建的一组蛋白质上验证了算法的正确性和准确性，并用于分析大组真实的蛋白质。验证集包含具有已知路径和宽度轮廓的人工创建孔的蛋白质。并将新算法与以前的基准算法HOLE进行了比较。结果表明，新算法的主要优点是，它可以成功地发现和表征隧道没有先验的指导或线索的位置的隧道口，它将成功地发现多个隧道，如果存在。CHUNNEL也可以与HOLE结合使用，前者用于为HOLE灌注，后者用于跟踪和表征孔隙。对从蛋白质数据库中挑选的膜蛋白结构家族以及具有预测的膜-水相界面的一组跨膜蛋白进行了分析，产生了第一个完全自动化的通过膜蛋白的隧道检查，包括在膜双层中退出的隧道。
We describe anew algorithm, CHUNNEL, to automatically find, characterize, and display tunnels or pores in proteins. The correctness and accuracy of the algorithm is verified on a constructed set of proteins and used to analyze large sets of real proteins. The verification set contains proteins with artificially created pores of known path and width profile. The previous benchmark algorithm, HOLE, is compared with the new algorithm. Results show that the major advantage of the new algorithm is that it can successfully find and characterize tunnels with no a priori guidance or clues about the location of the tunnel mouth, and it will successfully find multiple tunnels if present. CHUNNEL can also be used in conjunction with HOLE, with the former used to prime HOLE and the latter to track and characterize the pores. Analysis was conducted on families of membrane protein structures culled from the Protein Data Bank as well as on a set of transmembrane proteins with predicted membrane-aqueous phase interfaces, yielding the first completely automated examination of tunnels through membrane proteins, including tunnels that exit in the membrane bilayer.