Open-Protac-INVENT

Source code for our paper "---". This adaptation is built on top of Protac-invent (https://github.com/jidushanbojue/Protac-invent), which itself is based on REINVENT, reinvent-scoring, and DockStream.

This adaptation also integrates Roshambo (https://github.com/molecularinformatics/roshambo) to enable shape-based scoring functionality. We thank the original authors of all these projects for sharing their work.

Description

Open-Protac-INVENT is an open-source adaptation of Protac-Invent, designed for PROTAC linker generation using reinforcement learning and docking-based scoring. The original Protac-Invent framework combines generative modeling from REINVENT with scoring functions from reinvent-scoring and docking workflows from DockStream to enable reinforcement learning-driven linker design.

In this adaptation, we replace proprietary shape-similarity components (e.g., ROCS, Omega) with fully open-source alternatives using Roshambo and RDKit for 2D-to-3D conformer generation, shape-based scoring, and energy minimization. These modifications make the workflow more accessible and reproducible, allowing it to be used without commercial licenses.

The repository includes:

• Updated pipelines for open-source shape similarity scoring (Roshambo + RDKit).
• Integration with DockStream for docking and post-docking analysis.
• Configurable JSON templates for custom linker generation tasks.
• Example datasets and results to help users reproduce the workflow.

Diagrams

Figure 1: Initial Integration Diagram (To be updated)

Figure 2: General workflow of Open-Protac-INVENT. Adapted from Protac-invent under Apache 2.0 License.

Installation

1. Prerequisites

• Install Conda
• Ensure git is installed and available in your PATH.

2. Clone This Repository

$ git clone https://github.com/SaiCharithReddy/Open-Protac-INVENT.git
$ cd Open-Protac-INVENT

3. Open terminal, navigate to the cloned repository, and create the Conda environment

$ conda env create -f environment.yml

4. Activate the Environment

$ conda activate open-protac-invent

5. Install This Repo

$ pip install -e .

Usage

1. Edit the Template JSON

• Locate the template JSON file (for example: results/LINK_invent/BTK/template.json).
• Modify the file and folder paths in the template as needed.
• Other parameters can remain unchanged for a standard run.

2. Run the Model

Execute the following command to start the run using the edited JSON:

$ python input.py template.json

License & Attribution

This project is licensed under the Apache License 2.0, except where otherwise noted.

Portions of the code, specifically under src/roshambo/, are derived from Roshambo and are licensed under the GNU General Public License v3.0 (GPL-3.0).
Modifications were made to integrate Roshambo into this project. Users must comply with both licenses where applicable.

Full license details can be found in the LICENSE file.
For the GPL-3.0 portion, see src/roshambo/LICENSE.

We also acknowledge upstream work:

• Protac-Invent
• reinvent-scoring
• DockStream
• REINVENT