Computer-Aided Drug-Design Platform using PyMOL

Download and Installation

The software package consists of currently two Python plugins (two additional will follow soon) and a settings file containing information about the location of external software and used databases. The plugins should be viewed as interface between the GUI PyMOL to view, prepare and analyze protein-ligand complexes, and molecular modeling software to perform computations and simulations on the protein-ligand complexes. Thus, additional installation of external software is required to utilize our plugins. The current version of our plugins is designed for Linux OS.

Before downloading and installing our scripts, please download PyMOL from http://pymol.org and install it on your computer. The location of PyMOL will be noted as

$PyMOL

in the following.

The file Settings_Linux.txt needs to be downloaded and copied to your home directory.


Amber plugin

The plugin to perform molecular mechanics simulations using Amber can be downloaded here:

amber_Linux.py

It needs to be located in $PyMOL/modules/pmg_tk/startup/ where $PyMOL is the top-directory containing your local PyMOL installation.

The file AMBER_library.tar.gz needs to be downloaded (default to /usr/local) and extracted using

tar zxf AMBER_library.tar.gz

Prerequisites

To utilize the plugin, the following programs have to be installed:

Molecular mechanics program Amber and AmberTools

Our plugin has beed tested with AmberTools 1.2 and Amber10 (http://ambermd.org).

First, install AmberTools using the default location /usr/local/amber10. Please specify the environment variable AMBERHOME=/usr/local/amber10 (We added the variable to the .bashrc file, as we are using bash as default shell).

Install Amber to the same location (default: /usr/local/amber10).

File format conversion: Open Babel

To convert between different file formats our plugins use Open Babel (http://openbabel.org/wiki/Get_Open_Babel).

Our plugins have been tested with the source package of Open Babel 2.3.1.

Protein preparation: Reduce

To add hydrogens to the protein and optimize its hydrogen-bond network we make use of the program Reduce. Please download and install Reduce from http://kinemage.biochem.duke.edu/software/reduce.php. The executable has to be named reduce.

Our plugin has been tested with Reduce 3.14. We downloaded the src distribution to /usr/local/reduce, untared the file and used the Makefile (type make) in the directory reduce.3.14.080821.src . The executable will be located in the subdirectory reduce_src with the default name reduce.

Free energy calculation: SIE

Free energy analysis based on an AMBER protein-ligand MD trajectory can optionally be performed using Solvent Interaction Energy analysis with sietraj (http://www2.bri.nrc.ca/ccb/pub/sietraj_main.php).

Free energy calculation: MMPBSA

We use the MMPBSA module of Amber 10 together with the method of J. Kongsted and U. Ryde to compute the change in entropy upon ligand binding (http://www.teokem.lu.se/~ulf/Methods/mm_pbsa.html). The programs changepdb and changecrd need to be requested directly from Dr. Ryde.


AutoDock Vina plugin

The plugin to perform docking using AutoDock Vina can be downloaded here:

AutoDockVina.py

It needs to be located in $PyMOL/modules/pmg_tk/startup/ where $PyMOL is the top-directory containing your local PyMOL installation.

Prerequisites

To utilize the plugin, the following programs have to be installed:

Docking program AutoDock Vina and MGLTools

Our plugin has beed tested with AutoDock Vina 1.1.2 (http://vina.scripps.edu) and MGLTools 1.5.4 (http://mgltools.scripps.edu/downloads).


Slide plugin

We are currently adjusting the script to the current version of Slide. An updated version will be available as soon as possible.


QSAR plugin

... will follow.