Scaffold hopping by holistic molecular descriptors in drug design

Preliminary steps

In order to download and run the code, ensure you have the following software on your machine:

• Anaconda (for Python 3.7): www.anaconda.com
• Git: https://www.atlassian.com/git/tutorials/install-git.

Getting the code

Clone the repository, as follows:

git clone https://github.com/grisoniFr/scaffold_hopping_whales

A copy of the repository will be generated on your local machine, in the dedicated GitHub folder. Move to the donwloaded repository to start using it.

Setting up the virtual environment

Performing all the calculations within a virtual environment is recommended. You can import the environment information (as provided in the “scaffold_hopping.yml” file) as follows:

conda env create -f scaffold_hopping.yml

To use the installed packages, activate the environment:

conda activate scaffold_hopping

Use the provided Jupyter notebook

Move to the code folder, where the Jupyter notebook file is contained, and launch Jupter Notebook, as follows:

jupyter notebook

Click on the notebook file "virtual_screening_pipeline.jpynb". There, you will find additional information on the required calculation steps.

Use the provided Python script

Move to the code folder, where the Python scripts are contained. Please review the Jupyter notebook to understand the workflow and the output. Then run the script with Python:

python run.py library_file.sdf molecule_file.txt settings_file.txt

Pass file paths as arguments. Example data is in the data folder. Then just wait for the program to finish running. The program will generate results in the output folder.

If your systems has display, you can also run the script as follows:

python run_with_display.py

Three file selection dialog boxes will pop up asking you to select files. Select the library file (.sdf), reference molecule file (.sdf or .txt), and settings file (.txt, optional) in that order. Example files are located in the data folder.

Notes:

• Use plain text file for SMILES string input and settings
• Refer to the settings file for configuration details

How to cite

If you use this code or parts thereof, please cite the following papers:

• Grisoni F, Merk D, Consonni V, Hiss J.A, Giani Tagliabue S, Todeschini R, Schneider G. "Scaffold hopping from natural products to synthetic mimetics by holistic molecular similarity". Communications Chemistry 2018, 1, 1-9. https://www.nature.com/articles/s42004-018-0043-x
• Grisoni F, Schneider G. "Molecular scaffold hopping via holistic molecular representation", 2020, In: Protein-Ligand Interactions and Drug Design (Eds: F. Ballante), Methods in Molecular Biology (in press).