COMmunication MApping v2.0

A method to identify highly sensitive residues and predicts deleterious mutations.

alt text Proteins adapt to environmental conditions by changing their shape and motions. Characterising protein conformational dynamics is increasingly recognised as necessary to understand how proteins function. Given a conformational ensemble, computational tools are needed to extract in a systematic way pertinent and comprehensive biological information. Communication Mapping (COMMA) was developed to decipher the dynamical architecture of a protein [1]. The method first extracts residue-based dynamic properties from all-atom molecular dynamics simulations. Then, it integrates them in a graph theoretic framework, where it identifies groups of residues or protein regions that mediate allosteric communication. COMMA introduced original concepts to contrast the different roles played by these regions, namely communication blocks and communicating segment pairs, and evaluated the connections and communication strengths between them. In COMMA2 [2], these concepts are used to predict the impact of a residue mutation and highly sensitive residues to mutations. COMMA2 is a fully automated tool with broad applicability and is freely available to the community.

Download

The COMMA2 package is available here.

System Requirements

  • UNIX platform (Linux/OSX) and a GCC compiler.
  • Python, version 3, available at https://www.python.org/
  • Eigen, a C++ library for linear algebra.
  • MDTraj, a python library to analyse MD simulation trajectories.

    McGibbon RT, Beauchamp KA, Harrigan MP, Klein C, Swails JM, Hernández CX, Schwantes CR, Wang LP, Lane TJ, Pande VS. (2015) Biophysical journal., 109:1528-1532

  • Numpy python package
  • Networkx python package
  • PyMol (external tool).

    • DeLano WL. (2002), The pymol molecular graphics system.

Installation

  1. Unzip the COMMA2.zip in the directory of your choice.
  2. Add COMMA_HOME to system variables, it should point to the unzipped directory.
  3. Install the software using "pip install . --user" or "pip install . " if you have administration priviledges or if you are working in a python virtual environment (recommended)

Instruction for running COMMA2

  1. The instructions for running and installing COMMA2 can be found in the README file.
  2. An example of a command line to execute COMMA2 is:
  3. python $COMMA_HOME/src/comma_manager.py -t $data_path/1BDD_20_50_1.binpos $data_path/1BDD_20_50_2.binpos -p $data_path/1BDD_20_50.pdb -w $comma_workdir

After the execution, in the specified data path, 2 folders will be created by COMMA2, 1) Parameters, where all the parameters measured/used by COMMA2 are placed in and 2) Results, that contains all the generated outputs: adjacency matrices for the PCN and pathway-based and clique-based connected components, all pairs of communicating segments, their direct contact and a list of their strenghts and the average structure for each replicate.

Two pml scripts can be generated using the pymol_interface.py script for the system (cf README):

  1. StructureName_ComBlocks.pml: to visualize all connected components and Cliques on the structure in pymol.
  2. StructureName_SegPairs.pml: to visualize all pairs of communicating segments and their direct contact in pymol.

Licence

The COMMA2 package has been developed under the CeCILL licence (see LICENCE).

Contact

For questions, comments or suggestions feel free to contact Yasaman Karami, Tristan Bitard-Feildel, Elodie Laine, or Alessandra Carbone.

Reference

If you use COMMA2, please cite:

[1] Y. Karami, E. Laine and A. Carbone, Dissecting protein architecture with communication blocks and communicating segment pairs, BMC bioinformatics 17.2 (2016).

[2] Y. Karami, T. Bitard-Feildel, E. Laine and A. Carbone, "Infostery" analysis of protein dynamics identifies highly sensitive residues and predicts deleterious mutation, submitted.