eTOX ALLIES is an open source framework that allows the automated prediction of ligand-binding free energies requiring the ligand structure as only input. eTOX ALLIES is based on the Linear Interaction Energy (LIE) approach, an efficient end-point free energy method derived from Free Energy Perturbation (FEP) theory. Upon submission of a ligand or dataset of compounds, the tool performs the multiple steps required for binding free-energy prediction (docking, ligand topology creation, molecular dynamics simulations, data analysis), making use of external open source software where necessary. Moreover, functionalities are also available to enable and assist the creation and calibration of new models. In addition, a web graphical user interface (GUI) has been developed to allow use of free-energy based models to users that are not an expert in molecular modeling.
eTOX ALLES depends on external software for the key stages in the ligand-binding free energy predictions:
- Topology generation: AMBERTOOLS and ACPYPE
- Docking: PLANTS or ParaDocks
- Molecular Dynamics: GROMACS
The topology and docking stages are executed on the local machine and require the software to be available and the path to the executables defined in the eTOXlie/data/settings.json configuration file.
GROMACS molecular dynamics calculations can be offloaded to an external cluster using an SSH connection. Configuration of the SSH connection, cluster queueing system and external GROMACS executables should be defined in the eTOXlie/data/settings.json configuration file.
The eTOXlie installer will try to auto detect prerequisites but a manual check is recommended.
The eTOX ALLIES Python code uses a number of third-party Python packages. The easiest way to install eTOX ALLIES and respect Python dependencies is to use the Python virtual environment. This will install all Python dependencies in a Python virtual environment from the Python package repository (pip).
To install using the virtual environment run the eTOX ALLIES installer under bash as:
>> ./installer.sh -s
If you are using Anaconda or Miniconda to manage your Python environment please use the -c option for the installer
to have eTOX ALLIES use the conda command for installation.
>> ./installer.sh -s -c
The second option is to install eTOX ALLIES without the virtual environment in wich case you are responsible for installing third-party Python packages yourself. The required Python dependencies are listed in the Pipfile.
To install without the use of the virtual environment run the eTOX ALLIES installer under bash as:
>> ./installer.sh -s -n
NOTE
Please note that the packages installed via pip need the python development headers installed (python-dev)
Application configuration is defined in the eTOXlie/data/settings.json file. Use this file to define eTOXlie application settings, paths to external dependancies and connection to external clusters for GROMACS calculations.
Documentation on the use of the eTOX ALLIES web based graphical user interface is included in the package as the eTOX_ALLIES_GUI.docx Word document
If you have been using eTOX ALLIES please cite it using the following reference:
L. Capoferri et al. "eTOX ALLIES: an Automated pipeLine for Linear Interaction Energy-based Simulations", (2017) J. Cheminf.