datamol

# Datamol Cheminformatics Skill ## Overview Datamol is a Python library that provides a lightweight, Pythonic abstraction layer over RDKit for molecular cheminformatics. Simplify complex molecular operations with sensible defaults, efficient parallelization, and modern I/O capabilities. All molecular objects are native `rdkit.Chem.Mol` instances, ensuring full compatibility with the RDKit ecosystem. **Key capabilities**: - Molecular format conversion (SMILES, SELFIES, InChI) - Structure standardization and sanitization - Molecular descriptors and fingerprints - 3D conformer generation and analysis - Clustering and diversity selection - Scaffold and fragment analysis - Chemical reaction application - Visualization and alignment - Batch processing with parallelization - Cloud storage support via fsspec ## Installation and Setup Guide users to install datamol: ```bash uv pip install datamol ``` **Import convention**: ```python import datamol as dm ``` ## Core Workflows ### 1. Basic Molecule Handling **Creating molecules from SMILES**: ```python import datamol as dm # Single molecule mol = dm.to_mol("CCO") # Ethanol # From list of SMILES smiles_list = ["CCO", "c1ccccc1", "CC(=O)O"] mols = [dm.to_mol(smi) for smi in smiles_list] # Error handling mol = dm.to_mol("invalid_smiles") # Returns None if mol is None: print("Failed to parse SMILES") ``` **Converting molecules to SMILES**: ```python # Canonical SMILES smiles = dm.to_smiles(mol) # Isomeric SMILES (includes stereochemistry) smiles = dm.to_smiles(mol, isomeric=True) # Other formats inchi = dm.to_inchi(mol) inchikey = dm.to_inchikey(mol) selfies = dm.to_selfies(mol) ``` **Standardization and sanitization** (always recommend for user-provided molecules): ```python # Sanitize molecule mol = dm.sanitize_mol(mol) # Full standardization (recommended for datasets) mol = dm.standardize_mol( mol, disconnect_metals=True, normalize=True, reionize=True ) # For SMILES strings directly clean_smiles = dm.standardize_smiles(smiles) ``` ### 2. Reading and Writing Molecular Files Refer to `references/io_module.md` for comprehensive I/O documentation. **Reading files**: ```python # SDF files (most common in chemistry) df = dm.read_sdf("compounds.sdf", mol_column='mol') # SMILES files df = dm.read_smi("molecules.smi", smiles_column='smiles', mol_column='mol') # CSV with SMILES column df = dm.read_csv("data.csv", smiles_column="SMILES", mol_column="mol") # Excel files df = dm.read_excel("compounds.xlsx", sheet_name=0, mol_column="mol") # Universal reader (auto-detects format) df = dm.open_df("file.sdf") # Works with .sdf, .csv, .xlsx, .parquet, .json ``` **Writing files**: ```python # Save as SDF dm.to_sdf(mols, "output.sdf") # Or from DataFrame dm.to_sdf(df, "output.sdf", mol_column="mol") # Save as SMILES file dm.to_smi(mols, "output.smi") # Excel with rendered molecule images dm.to_xlsx(df, "output.xlsx", mol_columns=["mol"]) ``` **Remote file support** (S3, GCS, HTTP): ```python # Read from cloud storage df = dm.read_sdf("s3://bucket/compounds.sdf") df = dm.read_csv("https://example.com/data.csv") # Write to cloud storage dm.to_sdf(mols, "s3://bucket/output.sdf") ``` ### 3. Molecular Descriptors and Properties Refer to `references/descriptors_viz.md` for detailed descriptor documentation. **Computing descriptors for a single molecule**: ```python # Get standard descriptor set descriptors = dm.descriptors.compute_many_descriptors(mol) # Returns: {'mw': 46.07, 'logp': -0.03, 'hbd': 1, 'hba': 1, # 'tpsa': 20.23, 'n_aromatic_atoms': 0, ...} ``` **Batch descriptor computation** (recommended for datasets): ```python # Compute for all molecules in parallel desc_df = dm.descriptors.batch_compute_many_descriptors( mols, n_jobs=-1, # Use all CPU cores progress=True # Show progress bar ) ``` **Specific descriptors**: ```python # Aromaticity n_aromatic = dm.descriptors.n_aromatic_atoms(mol) aromatic_ratio = dm.descriptors.n_aromatic_atoms_proportion(mol) # Stereochemistry n_stereo = dm.descriptors.n_stereo_centers(mol) n_unspec = dm.descriptors.n_stereo_centers_unspecified(mol) # Flexibility n_rigid = dm.descriptors.n_rigid_bonds(mol) ``` **Drug-likeness filtering (Lipinski's Rule of Five)**: ```python # Filter compounds def is_druglike(mol): desc = dm.descriptors.compute_many_descriptors(mol) return ( desc['mw'] <= 500 and desc['logp'] <= 5 and desc['hbd'] <= 5 and desc['hba'] <= 10 ) druglike_mols = [mol for mol in mols if is_druglike(mol)] ``` ### 4. Molecular Fingerprints and Similarity **Generating fingerprints**: ```python # ECFP (Extended Connectivity Fingerprint, default) fp = dm.to_fp(mol, fp_type='ecfp', radius=2, n_bits=2048) # Other fingerprint types fp_maccs = dm.to_fp(mol, fp_type='maccs') fp_topological = dm.to_fp(mol, fp_type='topological') fp_atompair = dm.to_fp(mol, fp_type='atompair') ``` **Similarity calculations**: ```python # Pairwise distances within a set distance_matrix = dm.pdist(mols, n_jobs=-1) # Distances between two sets distances = dm.cdist(query_mols, library_mols, n_jobs=-1) # Find most similar molecules from scipy.spatial.distance import squareform dist_matrix = squareform(dm.pdist(mols)) # Lower distance = higher similarity (Tanimoto distance = 1 - Tanimoto similarity) ``` ### 5. Clustering and Diversity Selection Refer to `references/core_api.md` for clustering details. **Butina clustering**: ```python # Cluster molecules by structural similarity clusters = dm.cluster_mols( mols, cutoff=0.2, # Tanimoto distance threshold (0=identical, 1=completely different) n_jobs=-1 # Parallel processing ) # Each cluster is a list of molecule indices for i, cluster in enumerate(clusters): print(f"Cluster {i}: {len(cluster)} molecules") cluster_mols = [mols[idx] for idx in cluster] ``` **Important**: Butina clustering builds a full distance matrix - suitable for ~1000 molecules, not for 10,000+. **Diversity selection**: ```python # Pick diverse subset diverse_mols = dm.pick_diverse( mols, npick=100 # Select 100 diverse molecules ) # Pick cluster centroids centroids = dm.pick_centroids( mols, npick=50 # Select 50 representative molecules ) ``` ### 6. Scaffold Analysis Refer to `references/fragments_scaffolds.md` for complete scaffold documentation. **Extracting Murcko scaffolds**: ```python # Get Bemis-Murcko scaffold (core structure) scaffold = dm.to_scaffold_murcko(mol) scaffold_smiles = dm.to_smiles(scaffold) ``` **Scaffold-based analysis**: ```python # Group compounds by scaffold from collections import Counter scaffolds = [dm.to_scaffold_murcko(mol) for mol in mols] scaffold_smiles = [dm.to_smiles(s) for s in scaffolds] # Count scaffold frequency scaffold_counts = Counter(scaffold_smiles) most_common = scaffold_counts.most_common(10) # Create scaffold-to-molecules mapping scaffold_groups = {} for mol, scaf_smi in zip(mols, scaffold_smiles): if scaf_smi not in scaffold_groups: scaffold_groups[scaf_smi] = [] scaffold_groups[scaf_smi].append(mol) ``` **Scaffold-based train/test splitting** (for ML): ```python # Ensure train and test sets have different scaffolds scaffold_to_mols = {} for mol, scaf in zip(mols, scaffold_smiles): if scaf not in scaffold_to_mols: scaffold_to_mols[scaf] = [] scaffold_to_mols[scaf].append(mol) # Split scaffolds into train/test import random scaffolds = list(scaffold_to_mols.keys()) random.shuffle(scaffolds) split_idx = int(0.8 * len(scaffolds)) train_scaffolds = scaffolds[:split_idx] test_scaffolds = scaffolds[split_idx:] # Get molecules for each split train_mols = [mol for scaf in train_scaffolds for mol in scaffold_to_mols[scaf]] test_mols = [mol for scaf in test_scaffolds for mol in scaffold_to_mols[scaf]] ``` ### 7. Molecular Fragmentation Refer to `references/fragments_scaffolds.md` for fragmentation details. **BRICS fragmentation** (16 bond types): ```python # Fragment molecule fragments = dm.fragment.brics(mol) # Returns: set of fragment SMILES with attachment points like '[1*]CCN' ``` **RECAP fragmentation** (11 bond types): ```python fragments = dm.fragment.recap(mol) ``` **Fragment analysis**: ```python # Find common fragments across compound library from collections import Counter all_fragments = [] for mol in mols: frags = dm.fragment.brics(mol) all_fragments.extend(frags) fragment_counts = Counter(all_fragments) common_frags = fragment_counts.most_common(20) # Fragment-based scoring def fragment_score(mol, reference_fragments): mol_frags = dm.fragment.brics(mol) overlap = mol_frags.intersection(reference_fragments) return len(overlap) / len(mol_frags) if mol_frags else 0 ``` ### 8. 3D Conformer Generation Refer to `references/conformers_module.md` for detailed conformer documentation. **Generating conformers**: ```python # Generate 3D conformers mol_3d = dm.conformers.generate( mol, n_confs=50, # Number to generate (auto if None) rms_cutoff=0.5, # Filter similar conformers (Ångströms) minimize_energy=True, # Minimize with UFF force field method='ETKDGv3' # Embedding method (recommended) ) # Access conformers n_conformers = mol_3d.GetNumConformers() conf = mol_3d.GetConformer(0) # Get first conformer positions = conf.GetPositions() # Nx3 array of atom coordinates ``` **Conformer clustering**: ```python # Cluster conformers by RMSD clusters = dm.conformers.cluster( mol_3d, rms_cutoff=1.0, centroids=False ) # Get representative conformers centroids = dm.conformers.return_centroids(mol_3d, clusters) ``` **SASA calculation**: ```python # Calculate solvent accessible surface area sasa_values = dm.conformers.sasa(mol_3d, n_jobs=-1) # Access SASA from conformer properties conf = mol_3d.GetConformer(0) sasa = conf.GetDoubleProp('rdkit_free_sasa') ``` ### 9. Visualization Refer to `references/descriptors_viz.md` for visualization documentation. **Basic molecule grid**: ```python # Visualize molecules dm.viz.to_image( mols[:20], legends=[dm.to_smiles(m) for m in mols[:20]], n_cols=5, mol_size=(300, 300) ) # Save to file dm.viz.to_image(mols, outfile="molecules.png") # SVG for publications dm.viz.to_image(mols, outfile="molecules.svg", use_svg=True) ``` **Aligned visualization** (for SAR analysis): ```python # Align molecules by common substructure dm.viz.to_image( similar_mols, align=True, # Enable MCS alignment legends=activity_labels, n_cols=4 ) ``` **Highlighting substructures**: ```python # Highlight specific atoms and bonds dm.viz.to_image( mol, highlight_atom=[0, 1, 2, 3], # Atom indices highlight_bond=[0, 1, 2] # Bond indices ) ``` **Conformer visualization**: ```python # Display multiple conformers dm.viz.conformers( mol_3d, n_confs=10, align_conf=True, n_cols=3 ) ``` ### 10. Chemical Reactions Refer to `references/reactions_data.md` for reactions documentation. **Applying reactions**: ```python from rdkit.Chem import rdChemReactions # Define reaction from SMARTS rxn_smarts = '[C:1](=[O:2])[OH:3]>>[C:1](=[O:2])[Cl:3]' rxn = rdChemReactions.ReactionFromSmarts(rxn_smarts) # Apply to molecule