csa3d 0.2.0__tar.gz

csa3d-0.2.0/LICENSE

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csa3d-0.2.0/PKG-INFO

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+Metadata-Version: 2.4
+Name: csa3d
+Version: 0.2.0
+Summary: Extract and analyze enzyme catalytic sites in 3D from the Mechanism and Catalytic Site Atlas (M-CSA)
+Author-email: Ioannis Riziotis <riziotis@ebi.ac.uk>
+License: Apache-2.0
+Project-URL: Homepage, https://github.com/your-username/csa3d
+Project-URL: Documentation, https://csa3d.readthedocs.io
+Project-URL: Repository, https://github.com/your-username/csa3d
+Project-URL: Issue Tracker, https://github.com/your-username/csa3d/issues
+Keywords: enzymes,catalysis,structural-biology,M-CSA,active-sites
+Classifier: Development Status :: 4 - Beta
+Classifier: Intended Audience :: Science/Research
+Classifier: License :: OSI Approved :: Apache Software License
+Classifier: Programming Language :: Python :: 3
+Classifier: Programming Language :: Python :: 3.8
+Classifier: Programming Language :: Python :: 3.9
+Classifier: Programming Language :: Python :: 3.10
+Classifier: Programming Language :: Python :: 3.11
+Classifier: Programming Language :: Python :: 3.12
+Classifier: Topic :: Scientific/Engineering :: Bio-Informatics
+Classifier: Topic :: Scientific/Engineering :: Chemistry
+Requires-Python: >=3.8
+Description-Content-Type: text/markdown
+License-File: LICENSE
+Requires-Dist: biopython>=1.81
+Requires-Dist: numpy>=1.21.0
+Requires-Dist: pandas>=1.3.0
+Requires-Dist: scipy>=1.7.0
+Requires-Dist: scikit-learn>=0.24.0
+Requires-Dist: rdkit>=2021.09.0
+Requires-Dist: natsort>=8.0.0
+Requires-Dist: dendrogram-cut>=0.1.0
+Requires-Dist: parity-core>=0.5.0
+Requires-Dist: rmsd>=1.4.0
+Provides-Extra: dev
+Requires-Dist: pytest>=7.0; extra == "dev"
+Requires-Dist: pytest-cov>=4.0; extra == "dev"
+Requires-Dist: black>=23.0; extra == "dev"
+Requires-Dist: isort>=5.12; extra == "dev"
+Requires-Dist: flake8>=6.0; extra == "dev"
+Requires-Dist: mypy>=1.0; extra == "dev"
+Requires-Dist: types-setuptools; extra == "dev"
+Requires-Dist: types-requests; extra == "dev"
+Provides-Extra: docs
+Requires-Dist: sphinx>=6.0; extra == "docs"
+Requires-Dist: sphinx-rtd-theme>=1.2; extra == "docs"
+Requires-Dist: myst-parser>=0.19; extra == "docs"
+Provides-Extra: examples
+Requires-Dist: jupyter>=1.0; extra == "examples"
+Requires-Dist: notebook>=6.0; extra == "examples"
+Requires-Dist: matplotlib>=3.5; extra == "examples"
+Dynamic: license-file
+
+# CSA-3D: 3D Analysis of Enzyme Catalytic Sites
+
+A Python package for extracting, analyzing, and manipulating enzyme catalytic sites in three dimensions from the **Mechanism and Catalytic Site Atlas (M-CSA)** hosted at [EMBL-EBI](https://www.ebi.ac.uk/thornton-srv/m-csa/).
+
+## What is CSA-3D?
+
+CSA-3D enables computational biochemists and structural biologists to:
+
+- **Extract** catalytic site geometries from PDB structures and UniProt sequences
+- **Compare** active sites across homologous proteins using RMSD clustering
+- **Create** structure templates for enzyme active sites with geometric constraints
+- **Analyze** ligand proximity and chemical similarity in active sites
+- **Visualize** and export catalytic site information in multiple formats
+
+This package was developed to support research on enzyme mechanisms and is particularly useful for:
+- Comparative structural analysis of enzyme families
+- Active site template generation for molecular docking
+- Catalytic site conservation studies
+- Structure-guided annotation of enzyme function
+
+**See also**: [CSA-3D paper](https://www.sciencedirect.com/science/article/pii/S0022283622000912)
+
+## Installation
+
+### Requirements
+
+- Python 3.8 or higher
+- ~50 GB of disk space for complete M-CSA dataset (can work with subsets)
+
+### Installation from PyPI
+
+```bash
+pip install csa3d
+```
+
+### Installation from Source
+
+```bash
+git clone https://github.com/your-username/csa3d.git
+cd csa3d
+pip install -e ".[dev]"
+```
+
+### Development Installation
+
+For development with testing and documentation tools:
+
+```bash
+pip install -e ".[dev,docs]"
+```
+
+## Quick Start
+
+### 1. Configure Data Directory
+
+First, you need to set up the M-CSA data files. You can either:
+
+**Option A: Download automatically (recommended)**
+```python
+from csa3d import config
+config.setup_data("/path/to/csa3d_data")  # Downloads ~50 GB
+```
+
+**Option B: Set environment variable**
+```bash
+export CSA3D_DATA_DIR="/path/to/csa3d_data"
+```
+
+**Option C: Set in code**
+```python
+from csa3d import config
+config.set_data_dir("/path/to/csa3d_data")
+```
+
+### 2. Load and Inspect Active Sites
+
+```python
+from csa3d import Mcsa
+
+# Initialize the database
+db = Mcsa()
+
+# Build a specific entry (e.g., M-CSA ID 1)
+db.build(entry_ids=1, annotate=True)
+
+# Iterate over entries
+for entry in db:
+    print(f"Entry {entry.mcsa_id}: {len(entry.pdbsites)} PDB sites")
+    
+    # Get information
+    print(f"  EC Number: {entry.info['ec']}")
+    print(f"  Enzyme: {entry.info['enzyme_name']}")
+    
+    # Inspect active sites
+    for site in entry.get_pdbsites(sane_only=True):
+        print(f"    PDB: {site.pdb_id}, {len(site.residues)} residues")
+        print(f"    Resolution: {site.resolution} Å")
+```
+
+### 3. Clustering and Template Creation
+
+```python
+# Build multiple entries
+db.build(entry_ids=[1, 2, 3], annotate=True)
+entry = db.entries[1]
+
+# Calculate RMSD between all active sites
+sites = list(entry.get_pdbsites(sane_only=True))
+rmsd_matrix = entry.rmsd_matrix(sites)
+
+# Cluster sites by similarity
+clusters = entry.clustering(rmsd_matrix, height=1.5)
+
+print(f"Found {len(clusters)} clusters")
+for cluster_id, site_ids in clusters.items():
+    print(f"  Cluster {cluster_id}: {len(site_ids)} sites")
+
+# Create a template from conserved sites
+template = entry.create_template(outdir="./templates")
+print(f"Template created: {template.id}")
+```
+
+## Data Requirements
+
+CSA-3D requires data from several external sources:
+
+### Core M-CSA Data
+- `mcsa/catalytic_residues_homologues.json` - Homologous catalytic residues
+- `mcsa/catalytic_residues_references.json` - Reference catalytic residues
+- `mcsa/entry_info/mcsa_entry_info.*.json` - Entry metadata
+
+### PDB Data
+- `pdbe/assembly_cif/cif/` - PDB assembly structures (mmCIF format)
+- `pdbe/pdb_ions.csv` - Ion classification
+- `pdbe/pdb_cofactors.csv` - Cofactor information
+- `pdbe/crystallization_hets.csv` - Crystallization artifacts
+
+### Sequence/Mapping Data (SIFTS)
+- `sifts/uniprot_pdb.csv` - UniProt to PDB mapping
+- `sifts/pdb_chain_uniprot.csv` - PDB to UniProt mapping
+- `sifts/pdb_chain_enzyme.csv` - PDB to EC number mapping
+
+### Reaction Data
+- `kegg/kegg_reaction_components.csv` - KEGG enzyme reactions
+- `rhea/rhea_reaction_components.csv` - RHEA reactions
+- `pdbe/resolu.idx` - PDB resolution index
+
+### Molecule Data
+- `kegg/sdf/` - KEGG small molecules
+- `chebi/sdf/` - ChEBI compounds
+- `pdbe/het_sdf/` - PDB heteroatom structures
+
+To download all data:
+```python
+from csa3d.config import setup_data
+setup_data("/path/to/csa3d_data")
+```
+
+Alternatively, download manually from:
+- M-CSA: https://www.ebi.ac.uk/thornton-srv/m-csa/download/
+- PDBe: https://www.ebi.ac.uk/pdbe/download/
+- SIFTS: https://www.ebi.ac.uk/pdbe/docs/sifts/
+- KEGG: https://www.kegg.jp/
+- RHEA: https://www.rhea-db.org/
+
+## Usage Examples
+
+### Comparing Two Active Sites
+
+```python
+from csa3d import Mcsa
+
+db = Mcsa()
+db.build(entry_ids=1)
+entry = db.entries[1]
+
+sites = list(entry.get_pdbsites(sane_only=True))
+if len(sites) >= 2:
+    site1, site2 = sites[0], sites[1]
+    
+    # Structural alignment
+    rotation, translation, rmsd_ca, rmsd_all = site1.fit(site2, weighted=True)
+    print(f"RMSD (backbone): {rmsd_ca:.2f} Å")
+    print(f"RMSD (all atoms): {rmsd_all:.2f} Å")
+```
+
+### Writing Templates for Docking
+
+```python
+# Create template with specific parameters
+template = entry.create_template(
+    ca=False,                    # Use all heavy atoms
+    outdir="./templates",
+    outfile="myenzyme.template.pdb",
+    all_fuzzy=False,            # Use conservative fuzzy matching
+    no_alt=False                # Include alternative residue options
+)
+
+# Template can be used with docking software like TESS/Jess
+```
+
+### Batch Processing
+
+```python
+from csa3d import Mcsa
+
+db = Mcsa()
+
+# Build all entries (takes time)
+entry_ids = list(db.catalytic_residue_info.keys())
+db.build(entry_ids=entry_ids[:10], verbose=True)  # First 10
+
+# Analyze
+for entry in db:
+    n_sites = len(entry.pdbsites)
+    n_clusters = len(entry.clustering(entry.rmsd_matrix(list(entry.get_pdbsites()))))
+    print(f"{entry.mcsa_id}: {n_sites} sites, {n_clusters} clusters")
+```
+
+## Key Classes
+
+### Mcsa
+Main database class. Load and manage M-CSA entries.
+```python
+db = Mcsa()
+db.build(entry_ids=1)  # Build specific entry
+entry = db.entries[1]  # Access Entry object
+```
+
+### Entry
+Represents one M-CSA entry containing PDB and UniProt active sites.
+```python
+entry.pdbsites           # List of PdbSite objects
+entry.unisites           # List of UniSite objects
+entry.create_template()  # Generate template
+entry.clustering()       # RMSD-based clustering
+```
+
+### PdbSite
+A catalytic site from a PDB structure.
+```python
+site.pdb_id              # PDB identifier
+site.residues            # Catalytic residues
+site.ligands             # Proximal ligands
+site.fit(other_site)     # Structural alignment
+```
+
+### UniSite
+A catalytic site from UniProt sequence.
+```python
+site.uniprot_id          # UniProt accession
+site.residues            # Catalytic residues
+```
+
+## Configuration
+
+### Environment Variables
+
+- `CSA3D_DATA_DIR` - Path to M-CSA data directory (default: auto-detect)
+
+### Configuration File
+
+Create `~/.csa3d/config.yml`:
+```yaml
+data_dir: /path/to/csa3d_data
+```
+
+### In Code
+
+```python
+from csa3d import config
+
+config.set_data_dir("/path/to/data")
+config.validate_config()  # Check if valid
+print(config.get_data_dir())
+```
+
+## Documentation
+
+- [Architecture Guide](docs/architecture.md) - System design and data flow
+- [API Reference](https://csa3d.readthedocs.io) - Full API documentation
+- [Examples](examples/) - Jupyter notebooks and scripts
+
+## Testing
+
+Run tests with pytest:
+```bash
+pytest tests/
+```
+
+Run with coverage:
+```bash
+pytest --cov=csa3d tests/
+```
+
+## Performance Considerations
+
+- **First run** is slow (~minutes) as PDB structures are parsed and cached
+- **RMSD clustering** on large site sets can be memory-intensive
+- **Template creation** involves fitting multiple structures (depends on cluster size)
+
+Tips:
+- Use `sane_only=True` to filter low-quality sites
+- Process entries in batches
+- Use `resolution_cutoff` to filter low-resolution structures
+- Cache parsed entries with pickle for reuse
+
+## Citation
+
+If you use CSA-3D in your research, please cite:
+
+```bibtex
+@article{Riziotis2022,
+    title={CSA-3D: {A} framework to manipulate enzyme catalytic sites in three dimensions},
+    author={Riziotis, Ioannis and others},
+    journal={Journal of Molecular Biology},
+    volume={434},
+    number={5},
+    pages={167488},
+    year={2022},
+    issn={0022-2836},
+    doi={10.1016/j.jmb.2022.167488},
+    url={https://www.sciencedirect.com/science/article/pii/S0022283622000912}
+}
+```
+
+## Contributing
+
+Contributions are welcome! Please:
+
+1. Fork the repository
+2. Create a feature branch: `git checkout -b feature/my-feature`
+3. Make changes and add tests
+4. Run quality checks: `make lint`
+5. Submit a pull request
+
+## Issues & Support
+
+- **Bug reports**: [GitHub Issues](https://github.com/your-username/csa3d/issues)
+- **Questions**: Create a discussion or post an issue
+- **Feature requests**: Open an issue with `[FEATURE]` prefix
+
+## License
+
+Apache License 2.0 - see LICENSE file for details
+
+## Contact
+
+- **Author**: Ioannis Riziotis
+- **Email**: riziotis@ebi.ac.uk
+- **Affiliation**: EMBL-EBI, Wellcome Trust Genome Campus, Cambridge, UK
+
+## Acknowledgments
+
+CSA-3D is built on top of several excellent packages:
+- [Biopython](https://biopython.org/) - Biological computation
+- [NumPy](https://numpy.org/) - Numerical computing
+- [SciPy](https://scipy.org/) - Scientific computing
+- [scikit-learn](https://scikit-learn.org/) - Machine learning
+- [RDKit](https://www.rdkit.org/) - Cheminformatics
+
+## Changelog
+
+See [CHANGELOG.md](CHANGELOG.md) for version history and breaking changes.
+
+---
+
+**Questions?** See [docs/faq.md](docs/faq.md) or open an issue.