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
cPEPmatch is a Python tool designed to find cyclic peptides that mimic proteins and target their binding partners. The program consists of four steps:
-
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.
-
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.
-
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.
-
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.
-
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.
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.
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).
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
- 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 the necessary Python packages using the requirements.txt file:
pip install -r requirements.txt
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.
- 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.
- Make cPEPmatch Executable Navigate to the cPEPmatch directory and make the main script executable:
chmod +x cPEPmatch.py
- Add cPEPmatch to PATH For convenience, add cPEPmatch to your system's PATH:
echo 'export PATH="$PATH:/path/to/cPEPmatch"' >> ~/.bashrc
source ~/.bashrc
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
Check out our full tutorial for a comprehensive guide with a practical example.