syndirella 5.0.0a0

Synthetically Driven Elaborations

Syndirella (Synthesis Directed Elaborations) is a tool for generating and scoring synthetically practical elaborations of molecules designed from fragment screens. Starting from the retrosynthetic analysis of fragment merged molecules, superstructures of the original reactants are found by catalog search and filtered by selectivity issues. The elaborated final products are defined by reaction SMIRKS patterns and energy minimized in the protein with restraints to experimental data.

Preprint: https://chemrxiv.org/engage/chemrxiv/article-details/68d4f08ff416303770403a44

Documentation

Full Documentation - Complete user guide, API reference, and examples

Quick Start

Installation

conda create -n syndirella python=3.10
conda activate syndirella
pip install cgrtools --use-pep517
pip install syndirella

Basic Usage

1. Setup AiZynthFinder (required for retrosynthesis):

   ⚠️ WARNING: This step downloads large model files (~750MB total) if run the first time. These are required to run AiZynthFinder.

   Files will be downloaded to: [syndirella_package_path]/aizynth/

   syndirella setup-aizynth
   

2. Run the pipeline:

   syndirella run --input /absolute/path/to/input.csv --output /absolute/path/to/output_directory --templates /absolute/path/to/templates/ --hits_path /absolute/path/to/fragments.sdf
   

   Note: All paths must be absolute paths.

Example Input

Create a CSV file with your fragment data:

smiles,hit1,hit2,hit3,template,compound_set
O=C(NC1CC(C(F)(F)F)C1)c1cc2ccsc2[nH]1,Ax0556a,Ax0566a,,Ax0310a,my_compound_set
CC(=O)Nc1cc(CC(=O)NCC(NC(=O)CCl)c2cccnc2)c(NC(C)=O)nn1,1346a,,,Ax1346a,my_compound_set

Requirements

• Python 3.10
• RDKit
• AiZynthFinder
• Fragmenstein
• Additional dependencies (see pyproject.toml)

Learn More

• Examples - Jupyter notebooks and sample data
• User Guide - Detailed usage instructions
• Reaction Constants - Advanced reaction settings and options

License

This project is licensed under the MIT License.