ConfBuster - Open source tools for macrocycles conformational search and analysis

 

Dependencies

CORE

• Python 2.7 (https://www.python.org)
• NetworkX (tested with 1.11) (https://networkx.github.io)
• Pymol (≥ 1.8) (https://sourceforge.net/projects/pymol)
• Open Babel (≥ 2.4.1) (http://openbabel.org/wiki/Main_Page) The version of Open Babel should imperatively be 2.4.1. As indicated in the instruction, Eigen version 2 is requiered to use properly Open Babel (https://openbabel.org/docs/dev/Installation/install.html). Link to download: https://sourceforge.net/projects/openbabel/files/

For a clean and functional installation:

In openbabel-2.4.1 directory:
$ mkdir build
$ cd build
$ cmake ../ -DCMAKE_INSTALL_PREFIX=/path/to/where/you/want
$ make -j4
$ make install
(This is essential for Open Babel to work properly)

OPTIONAL (VISUALISATION)

• R (≥ 3.0.0) (https://cran.r-project.org/index.html)
• R package ComplexHeatmap (≥ 1.14) (from Bioconductor release 3.5 (bioconductor.org))

R shell

source("http://bioconductor.org/biocLite.R")
biocLite("ComplexHeatmap")

• R package circlize (≥ 0.4.0)

R shell

install.packages("circlize")

Installation

The most simple way to install ConfBuster is by downloading the official release in the GitHub section "release". Alternatively, one may clone the ConfBuster repository using git :

$ git clone https://github.com/patricklague/ConfBuster.git

At your choice, put the scripts in a directory present in your $PATH OR add the directory where the scripts are to your $PATH:

export PATH=$PATH:/full-path-here/ConfBuster/

PyMOL and Open Babel should also be included in your $PATH. If you want to install them locally, you should change the headers of the ConfBuster scripts to add their correct absolute paths.

ConfBuster tools

• ConfBuster-Single-Molecule-Minimization Performs a simple minimization of the given molecule (recommended before).

-i input filename [mandatory]
-o output name prefix [default: replace input file]

• ConfBuster-Rotamer-Search Identify rotational isomers of a molecule.

-i input filename in mol2 [mandatory] 
-g number of generations [default: 100] 
-e the energy cutoff used to discriminate conformations in units of kcal/mol [default: 50]
-d output directory name [default: use the prefix of the input filename] 
-f format of outputted molecules [xyz or default: mol2]

• ConfBuster-Macrocycle-Linear-Sampling Performs a conformational search of a cyclic molecule.

-i input filename [mandatory]
-r rmsd cutoff in Angstrom [default: 0.5]
-n for each cleaving point, number of rotamer searches performed [default: 5] 
-N for each cleaving point, number of molecules extracted from each rotamer search [default: 5] 
-o output directory name [default: prefix of the input filename]

• ConfBuster-Analysis Perform post-analyses to visualize a clustering based on RMSD values between the conformations.

-i directory name of the search results [mandatory] 
-r rmsd cut off [default: none]
-n number of conformations to include in the analysis [default: all]
-e mid-point value of the energy color scale [default: 0]

Tutorial

Several examples including all the command lines and required files to run macrocyle conformational searches are included with the distribution, in the examples folder and in the examples/Instructions.pdf file.The user can follow this tutorial by using the molecule 1w96.pdb available in the directory examples/1w96. The initial structure is:

Step 1 Perform a single point optimisation on macro-1w96.pdb:

$ ConfBuster-Single-Molecule-Minimization.py -i macro-1w96.pdb

Step 2 Start Macrocyclic linear sampling:

$ ConfBuster-Macrocycle-Linear-Sampling.py -i macro-1w96.mol2 -n 5 -N 5 -r 0.5

Step 3 (Optional) View and analyse results:

$ cd macro-1w96
$ pymol Follow-macro-1w96.py

or alternatively, directly in Pymol:

run Follow-macro-1w96.py

The result should looks like:

Lowest energy conformation is in green (conf-16.mol2 in the matrix below). PDB structure is in cyan. RMSD between conf-16.mol2 and PDB structure is of 0.405 Angstrom over all atoms. All sampled conformations are in black thin lines to show the conformational range of the macrocycle.

Using the ConfBuster-Analysis.py module ($ ConfBuster-Analysis.py -i macro-1w96 -n 20) allows to compare the n best results with a reference or the initial structure. Results will be shown as a 2d RMSD matrix of n conformations. On the right, an energy bar (from green to purple) between the best and worst energy is displayed.

Other examples are provided in the directory "Examples"

How to cite ConfBuster

Barbeau, X., Vincent, A.T. & Lagüe, P., (2018). ConfBuster: Open-Source Tools for Macrocycle Conformational Search and Analysis. Journal of Open Research Software. 6(1), p.1. DOI: http://doi.org/10.5334/jors.189

License

ConfBuster Suite Copyright (C) 2017 Xavier Barbeau, Antony T. Vincent and Patrick Lagüe

This program is free software: you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version.

This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details.

You should have received a copy of the GNU General Public License along with this program. If not, see http://www.gnu.org/licenses/.