cPEPmatch

Created by: Brianda L. Santini

Supervised by: Prof. Dr. Martin Zacharias

Affiliation: Physics Department T38, Technical University of Munich, Garching, Germany.

Webserver version: cPEPmatch, Cite: Santini & Zacharias

General Description

cPEPmatch is a Python tool designed to find cyclic peptides that mimic proteins and target their binding partners. The program consists of four steps:

1. Cyclic Peptide Database Creation:

   • Reads from a pre-constructed database of 400 PDB structures downloaded from the PDB databank.
   • Characterizes motifs by calculating the CA carbon distances along the whole structure.
   • Users can select the motif size (4-7), consecutive or not, and specific features such as cyclization type or presence of non-standard amino acids.

2. Characterization of the Protein-Protein or Protein-Ligand Interface:

   • The motif is characterized using the same CA distance matrix as the cyclic peptide database.
   • Users can select the interface cutoff in angstroms and an optional parameter for protein-specific residues for targeted matching.

3. Backbone Match Motif:

   • Matches the CA distance motifs of the protein interface and the cyclic peptide database.
   • Selects matches that fit within the given frmsd_threshold and returns a Distance RMSD value in angstroms.

4. Superimpose and Mutate:

   • Matches are read and superimposed to match the structure of the protein mimic.
   • Returns a new Fit RMSD value in angstroms and mutates matching side-chains to mimic the protein.
   • Main limitation: Modeller cannot process non-standard residues, so these peptides are excluded from the mutation step.
   • Outputs a match_list.txt file and all mutated or aligned structures.

5. Results Analysis:

   • Output table contains match number, pdb name, Dist-RMSD, matched cyclic peptide residues, matched protein residues, Fit-RMSD, and file names.
   • Notebook version allows structure visualization by changing the match_to_view value.

Usage

Required Parameters

• pdb_name: PDB file name containing both the protein and the target.
• protein: Protein chain name.
• target: Target chain name.
• motif_size: Number of CA carbons to match.
• consecutive: Motif type (consecutive or non-consecutive).
• interface_cutoff: Distance in angstroms to define contact interface residues.
• frmsd_threshold: Fit-RMSD value in angstroms for matching precision.
• working_location: Path to the protein-target pdb file location.
• database_location: Path to the cPEPmatch database.

Optional Parameters

• protein_specific_residues: Residue numbers to match if known (e.g., from hot-spot analysis).
• cyclization_type: Specific cyclization type for cyclic peptides (e.g., 'head to tail').
• exclude_non_standard: Exclude non-standard amino acid containing peptides (default: False).

Directory Structure

cPEPmatch
├── cPEPmatch.py
├── cpep_modules
│ ├── backbone_match.py
│ ├── cpep_database.py
│ ├── protein_target_characterization.py
│ ├── superimpose_mutate.py
│ └── init.py
├── database
│ ├── cyclo_pep.csv
│ └── *.pdb
├── lib
│ ├── old_databases
│ ├── test_system
│ └── update_database
├── README.md
└── requirements.txt

Installation and Setup

Prerequisites

• Anaconda (recommended over Miniconda for compatibility reasons)

Creating a Conda Environment Create a dedicated Conda environment for cPEPmatch:

conda create -n "cpepmatch" python=3.7.11

conda activate cpepmatch

Install Required Python Packages

Install the necessary Python packages using the requirements.txt file:

  pip install -r requirements.txt

Install Additional Conda Modules

Some modules need to be installed specifically via Conda:

conda install -c conda-forge vmd.python

conda config --add channels salilab

conda install modeller

However, it will instruct you to modify /home/user/miniconda3/envs/server/lib/modeller-10.3/modlib/modeller/config.py and replace XXXX with your Modeller licence key (in this case: MODELIRANJE). Execute the command again.
If the installation of vmd-python doesn't work, go to https://github.com/Eigenstate/vmd-python, download the repo, and run it.

VMD-Python Installation Issues If you encounter issues installing vmd-python, visit vmd-python GitHub for alternative installation methods.

Making the Script Executable and Setting Up PATH

1. Update the Shebang Line Make sure the cpepmatch environment is activated Find the Path to the Python Interpreter: Use the which command to find out the path to the Python interpreter in the activated environment:

which python

This command will output the path to the Python interpreter, something like: /home/user/anaconda3/envs/cpepmatch/bin/python

Edit the cPEPmatch.py file to include the shebang line with the path to the Anaconda Python interpreter at the very top:

#!/home/user/anaconda3/envs/cpepmatch/bin/python

Replace the path with the one you obtained from the which python command.

2. Make cPEPmatch Executable Navigate to the cPEPmatch directory and make the main script executable:

chmod +x cPEPmatch.py

3. Add cPEPmatch to PATH For convenience, add cPEPmatch to your system's PATH:

echo 'export PATH="$PATH:/path/to/cPEPmatch"' >> ~/.bashrc
source ~/.bashrc

Usage

After installation, you can run cPEPmatch from any directory in your terminal:

cPEPmatch.py [arguments]

Replace [arguments] with appropriate command-line arguments for the script.

To learn about the various command-line arguments and options that cPEPmatch supports, you can use the help option:

cPEPmatch.py -h