PepLab

PepLab is a peptide library generation toolkit designed to support various workflows for processing peptide libraries, generating 3D structures, analyzing reactivity, planning reactions, and executing reactions. It provides a comprehensive platform for peptide-related research and analysis.

Key Features

• SMILES to Graph Conversion: Parse SMILES notation to create graph representations allowing for reaction modeling and combinatorial peptide library enumeration.
• 3D Structure Generation: Generate possible 3D structures using conformer generation, molecular dynamics (MD) simulation, or experimental structure loading.
• Reactivity Analysis: Calculate reactivity scores for reactive sites and generate possible reaction pathways.
• Reaction Planning: Evaluate reaction conditions and select the most viable pathways.
• Reaction Execution: Model bond formation and update electron positions to reflect new molecular structures.
• Library Assembly and Analysis: Generate peptide libraries, calculate properties, and store results.

Library Generation

Library generation in PepLab involves creating a diverse set of molecules that can be used for various applications such as virtual screening, drug design, and combinatorial chemistry.

Steps in Library Generation

1. Define Building Blocks:

   • Identify and list the core structures and fragments (building blocks) that will be used to create the library.

2. Combinatorial Enumeration:

   • Combine building blocks in all possible ways to generate a diverse set of molecules.

3. Filter and Optimize:

   • Apply filters
   • Optimize the library for specific properties (e.g., permeability, activity, mass differentiation).

4. Output Library:

   • Store the generated library in a suitable format (e.g. CSV, JSON, PDB, SDF, SMILES).

Molecular Graph Modeling

Molecular graph modeling in PepLab involves representing molecules as graphs where nodes represent atoms and edges represent bonds. This model allows for efficient manipulation and analysis of molecular structures.

Steps in Molecular Graph Modeling

1. Graph Construction:

   • Parse molecular representations (e.g., SMILES) to create a graph.

2. Graph Manipulation:

   • Perform operations like adding/removing atoms, modifying bonds, etc.

3. Graph Analysis:

   • Calculate molecular properties, identify substructures, etc.

Example Workflows

PepLab supports multiple workflows for processing peptide libraries. The existing workflows include:

1. Input Processing:

   • Handles library definition JSON and converts SMILES to graphs.
   • Processes residues and generates peptides directly.

2. Reactivity Analysis:

   • Calculates reactivity scores and generates possible pathways.
   • Applies temperature effects and scores pathway viability.

3. Reaction Planning:

   • Evaluates reaction conditions and selects preferred pathways.
   • Checks site compatibility and evaluates reaction conditions.

4. Reaction Execution:

   • Initializes selected reactions and checks spatial arrangements.
   • Begins bond formation, updates electron positions, and generates new molecules.

5. Library Assembly and Analysis:

   • Adds peptides to the library and calculates properties.

Contributing

Contributions are welcome! Here are the steps:

1. Fork the repository.
2. Create a new branch (git checkout -b feature-branch).
3. Make your changes.
4. Commit your changes (git commit -am 'Add new feature').
5. Push to the branch (git push origin feature-branch).
6. Create a new Pull Request.

License

This project is licensed under the MIT License. See the LICENSE file for more details.

Acknowledgements

• Andre