Kasahara Kota, Kinoshita Kengo
College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
Graduate School of Information Sciences, Tohoku University, Sendai, Miyagi, Japan.
PLoS One. 2016 Dec 1;11(12):e0167524. doi: 10.1371/journal.pone.0167524. eCollection 2016.
Ion conduction mechanisms of ion channels are a long-standing conundrum. Although the molecular dynamics (MD) method has been extensively used to simulate ion conduction dynamics at the atomic level, analysis and interpretation of MD results are not straightforward due to complexity of the dynamics. In our previous reports, we proposed an analytical method called ion-binding state analysis to scrutinize and summarize ion conduction mechanisms by taking advantage of a variety of analytical protocols, e.g., the complex network analysis, sequence alignment, and hierarchical clustering. This approach effectively revealed the ion conduction mechanisms and their dependence on the conditions, i.e., ion concentration and membrane voltage. Here, we present an easy-to-use computational toolkit for ion-binding state analysis, called IBiSA_tools. This toolkit consists of a C++ program and a series of Python and R scripts. From the trajectory file of MD simulations and a structure file, users can generate several images and statistics of ion conduction processes. A complex network named ion-binding state graph is generated in a standard graph format (graph modeling language; GML), which can be visualized by standard network analyzers such as Cytoscape. As a tutorial, a trajectory of a 50 ns MD simulation of the Kv1.2 channel is also distributed with the toolkit. Users can trace the entire process of ion-binding state analysis step by step. The novel method for analysis of ion conduction mechanisms of ion channels can be easily used by means of IBiSA_tools. This software is distributed under an open source license at the following URL: http://www.ritsumei.ac.jp/~ktkshr/ibisa_tools/.
离子通道的离子传导机制是一个长期存在的难题。尽管分子动力学（MD）方法已被广泛用于在原子水平上模拟离子传导动力学，但由于动力学的复杂性，MD结果的分析和解释并不简单。在我们之前的报告中，我们提出了一种称为离子结合状态分析的分析方法，通过利用各种分析协议，如复杂网络分析、序列比对和层次聚类，来仔细研究和总结离子传导机制。这种方法有效地揭示了离子传导机制及其对条件的依赖性，即离子浓度和膜电压。在这里，我们展示了一个用于离子结合状态分析的易于使用的计算工具包，称为IBiSA_tools。这个工具包由一个C++程序以及一系列Python和R脚本组成。用户可以根据MD模拟的轨迹文件和一个结构文件，生成离子传导过程的几个图像和统计数据。会以标准图形格式（图形建模语言；GML）生成一个名为离子结合状态图的复杂网络，它可以通过诸如Cytoscape等标准网络分析器进行可视化。作为一个教程，工具包还附带了Kv1.2通道50纳秒MD模拟的轨迹。用户可以逐步跟踪离子结合状态分析的整个过程。借助IBiSA_tools可以轻松使用这种分析离子通道离子传导机制的新方法。该软件根据开源许可在以下网址分发：http://www.ritsumei.ac.jp/~ktkshr/ibisa_tools/ 。
