IBiSA_Tools: A Computational Toolkit for Ion-Binding State Analysis in Molecular Dynamics Trajectories of Ion Channels

PLoS One. 2016 Dec 1;11(12):e0167524. doi: 10.1371/journal.pone.0167524. eCollection 2016.

Abstract

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/.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Cluster Analysis
  • Computer Graphics
  • Humans
  • Internet
  • Ion Channels / chemistry*
  • Ion Channels / metabolism
  • Ion Transport
  • Membrane Potentials / physiology*
  • Molecular Dynamics Simulation / statistics & numerical data*
  • Programming Languages
  • Protein Binding
  • Sequence Alignment
  • User-Computer Interface*

Substances

  • Ion Channels

Grant support

This work was funded by Japan Society for Promotion of Science, https://www.jsps.go.jp/english/index.html (grant numbers: 22136005, 15H02773, and 16K18526), and Japan Agency for Medical Research and Development (the project name is "the Platform Project for Supporting in Drug Discovery and Life Science Research"). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.