pdberellig 1.0.0

A toolkit for functional annotation of ligands in the PDB

PDBe RelLig

Relevant Ligands in PDB

With over 200,000 entries in the PDB, about 75% of these structures contain at least one ligand bound to a protein or nucleic acid. However, not all ligands are biologically relevant, some are present due to experimental necessities, such as aiding crystallisation or enabling cryoprotection, while others play biologically significant roles acting as cofactors, reactants or drugs. Unfortunately, the biological role of ligands present in PDB entries is not annotated in the PDB/mmCIF files. PDBe RelLig is designed to bridge this gap by automatically annotating the ligand's functional role as the following:

• cofactor
• reactant
• drug

Installation

Create and activate a virtual environment and then install PDBe RelLig

pip install pdberellig

Dependencies

• Python ^3.10
• click 8.1.7
• pdbeccdutils ^0.8.6
• sparqlwrapper ^2.0.0
• pandas ^2.2.3

Running the pipeline

There are three modes of pipelines:

cofactors

pdberellig cofactors --cif <path_to_ligand_cif_file> --ligand_type <type_of_ligand> --out-dir <path_to_output>

pipeline inputs

Options:
  --cif TEXT                   path to input cif file  [required]
  --ligand-type [CCD|PRD|CLC]  type of ligand in the PDB  [required]
  --out-dir TEXT               path to output directory  [required]
  --help                       Show this message and exit.

pipeline outputs

<ligand_id>_cofactor_annotation.json - a json file containing ligand interacting proteins and similarity to template and representative molecules of cofactor classes .

Example

{
    "HEM": {
        "template": {
            "id": "HEA",
            "similarity": 0.717
        },
        "representative": {
            "id": "HEA",
            "similarity": 0.717
        },
        "pdb_chains": [
            {
                "pdb_id": "3ks0",
                "auth_asym_id": "A",
                "struct_asym_id": "C",
                "uniprot_id": "P00175",
                "ec_number": "1.1.2.3"
            },
            {
                "pdb_id": "1ltd",
                "auth_asym_id": "A",
                "struct_asym_id": "A",
                "uniprot_id": "P00175",
                "ec_number": "1.1.2.3"
            },
        ]
    }
}

---

reactants

pdberellig reactants --cif <path_to_ligand_cif_file> --ligand_type <type_of_ligand> --chebi-structure-file <csv_file_with_chebi_mol> --out-dir <path_to_output>

pipeline inputs

Options:
  --cif TEXT                     path to input cif file  [required]
  --ligand-type [CCD|PRD|CLC]    type of ligand in the PDB  [required]
  --chebi-structure-file TEXT    Path to the ChEBI SDF file  [required]
  --out-dir TEXT                 path to output directory  [required]
  --update-chebi                 Path to the ChEBI archive files
  --minimal-ligand-size INTEGER  Minimum ligand size.  [default: 5]
  --help                         Show this message and exit.

pipeline outputs

<ligand_id>_reactant_annotation.tsv - A tsv file containing ligand interacting proteins and similarity to the reaction participants present in the reactions catalysed the protein

Example

pdb_id	auth_asym_id	struct_asym_id	uniprot_id	rhea_id	chebi_id	similarity
1r3q	A	A	P06132	19865	57308	0.714
1r3q	A	A	P06132	31239	62626	0.8
1r3q	A	A	P06132	31239	62631	1.0
1r3s	A	A	P06132	19865	57308	0.714
1r3s	A	A	P06132	31239	62626	0.8
1r3s	A	A	P06132	31239	62631	1.0
1r3v	A	A	P06132	19865	57308	0.714
1r3v	A	A	P06132	31239	62626	0.8
1r3v	A	A	P06132	31239	62631	1.0

---

drugs

pdberellig drugs --cif <path_to_ligand_cif_file> --ligand_type <type_of_ligand> --out-dir <path_to_output>

pipeline inputs

Options:
  --cif TEXT                   path to input cif file  [required]
  --out-dir TEXT               path to output directory  [required]
  --ligand-type [CCD|PRD|CLC]  type of ligand in the PDB  [required]
  --help                       Show this message and exit.

pipeline outputs

<ligand_id>_drug_annotation.tsv - a tsv file containing ligand interacting pharmacologically active drug-targets

Example

pdb_id	auth_asym_id	struct_asym_id	uniprot_id	name	organism
7n9g	A	A	P00519	Tyrosine-protein kinase ABL1	Humans
3pyy	B	B	P00519	Tyrosine-protein kinase ABL1	Humans
6npu	B	B	P00519	Tyrosine-protein kinase ABL1	Humans
6npe	A	A	P00519	Tyrosine-protein kinase ABL1	Humans
2hyy	A	A	P00519	Tyrosine-protein kinase ABL1	Humans
6npu	A	A	P00519	Tyrosine-protein kinase ABL1	Humans
6npv	B	B	P00519	Tyrosine-protein kinase ABL1	Humans
6npe	B	B	P00519	Tyrosine-protein kinase ABL1	Humans

Contribution

We encourage you to contribute to this project. The package uses poetry for packaging and dependency management. You can develop locally using:

git clone https://github.com/PDBeurope/rellig.git
cd rellig
pip install poetry
poetry install --with dev,doc
pre-commit install

The pre-commit hook will run linting, formatting and update poetry.lock. The poetry.lock file will lock all dependencies and ensure that they match pyproject.toml versions.

To add a new dependency

# Latest resolvable version
poetry add <package>

# Optionally fix a version
poetry add <package>@<version>

To change a version of a dependency, either edit pyproject.toml and run:

poetry sync --with dev

or

poetry add <package>@<version>

Documentation

The documentation is generated using sphinx in sphinx_rtd_theme and hosted on GitHub Pages. To generate the documentation locally,

cd doc
poetry run sphinx-build -b html . _build/html

# See the documentation at http://localhost:8080.
python -m http.server 8080 -d _build/html