@synsci/cli-darwin-x64-baseline 1.1.77 → 1.1.78

package/bin/skills/rdkit/scripts/molecular_properties.py

@@ -0,0 +1,243 @@
+#!/usr/bin/env python3
+"""
+Molecular Properties Calculator
+
+Calculate comprehensive molecular properties and descriptors for molecules.
+Supports single molecules or batch processing from files.
+
+Usage:
+    python molecular_properties.py "CCO"
+    python molecular_properties.py --file molecules.smi --output properties.csv
+"""
+
+import argparse
+import sys
+from pathlib import Path
+
+try:
+    from rdkit import Chem
+    from rdkit.Chem import Descriptors, Lipinski
+except ImportError:
+    print("Error: RDKit not installed. Install with: conda install -c conda-forge rdkit")
+    sys.exit(1)
+
+
+def calculate_properties(mol):
+    """Calculate comprehensive molecular properties."""
+    if mol is None:
+        return None
+
+    properties = {
+        # Basic properties
+        'SMILES': Chem.MolToSmiles(mol),
+        'Molecular_Formula': Chem.rdMolDescriptors.CalcMolFormula(mol),
+
+        # Molecular weight
+        'MW': Descriptors.MolWt(mol),
+        'ExactMW': Descriptors.ExactMolWt(mol),
+
+        # Lipophilicity
+        'LogP': Descriptors.MolLogP(mol),
+        'MR': Descriptors.MolMR(mol),
+
+        # Polar surface area
+        'TPSA': Descriptors.TPSA(mol),
+        'LabuteASA': Descriptors.LabuteASA(mol),
+
+        # Hydrogen bonding
+        'HBD': Descriptors.NumHDonors(mol),
+        'HBA': Descriptors.NumHAcceptors(mol),
+
+        # Atom counts
+        'Heavy_Atoms': Descriptors.HeavyAtomCount(mol),
+        'Heteroatoms': Descriptors.NumHeteroatoms(mol),
+        'Valence_Electrons': Descriptors.NumValenceElectrons(mol),
+
+        # Ring information
+        'Rings': Descriptors.RingCount(mol),
+        'Aromatic_Rings': Descriptors.NumAromaticRings(mol),
+        'Saturated_Rings': Descriptors.NumSaturatedRings(mol),
+        'Aliphatic_Rings': Descriptors.NumAliphaticRings(mol),
+        'Aromatic_Heterocycles': Descriptors.NumAromaticHeterocycles(mol),
+
+        # Flexibility
+        'Rotatable_Bonds': Descriptors.NumRotatableBonds(mol),
+        'Fraction_Csp3': Descriptors.FractionCsp3(mol),
+
+        # Complexity
+        'BertzCT': Descriptors.BertzCT(mol),
+
+        # Drug-likeness
+        'QED': Descriptors.qed(mol),
+    }
+
+    # Lipinski's Rule of Five
+    properties['Lipinski_Pass'] = (
+        properties['MW'] <= 500 and
+        properties['LogP'] <= 5 and
+        properties['HBD'] <= 5 and
+        properties['HBA'] <= 10
+    )
+
+    # Lead-likeness
+    properties['Lead-like'] = (
+        250 <= properties['MW'] <= 350 and
+        properties['LogP'] <= 3.5 and
+        properties['Rotatable_Bonds'] <= 7
+    )
+
+    return properties
+
+
+def process_single_molecule(smiles):
+    """Process a single SMILES string."""
+    mol = Chem.MolFromSmiles(smiles)
+    if mol is None:
+        print(f"Error: Failed to parse SMILES: {smiles}")
+        return None
+
+    props = calculate_properties(mol)
+    return props
+
+
+def process_file(input_file, output_file=None):
+    """Process molecules from a file."""
+    input_path = Path(input_file)
+
+    if not input_path.exists():
+        print(f"Error: File not found: {input_file}")
+        return
+
+    # Determine file type
+    if input_path.suffix.lower() in ['.sdf', '.mol']:
+        suppl = Chem.SDMolSupplier(str(input_path))
+    elif input_path.suffix.lower() in ['.smi', '.smiles', '.txt']:
+        suppl = Chem.SmilesMolSupplier(str(input_path), titleLine=False)
+    else:
+        print(f"Error: Unsupported file format: {input_path.suffix}")
+        return
+
+    results = []
+    for idx, mol in enumerate(suppl):
+        if mol is None:
+            print(f"Warning: Failed to parse molecule {idx+1}")
+            continue
+
+        props = calculate_properties(mol)
+        if props:
+            props['Index'] = idx + 1
+            results.append(props)
+
+    # Output results
+    if output_file:
+        write_csv(results, output_file)
+        print(f"Results written to: {output_file}")
+    else:
+        # Print to console
+        for props in results:
+            print("\n" + "="*60)
+            for key, value in props.items():
+                print(f"{key:25s}: {value}")
+
+    return results
+
+
+def write_csv(results, output_file):
+    """Write results to CSV file."""
+    import csv
+
+    if not results:
+        print("No results to write")
+        return
+
+    with open(output_file, 'w', newline='') as f:
+        fieldnames = results[0].keys()
+        writer = csv.DictWriter(f, fieldnames=fieldnames)
+        writer.writeheader()
+        writer.writerows(results)
+
+
+def print_properties(props):
+    """Print properties in formatted output."""
+    print("\nMolecular Properties:")
+    print("="*60)
+
+    # Group related properties
+    print("\n[Basic Information]")
+    print(f"  SMILES:              {props['SMILES']}")
+    print(f"  Formula:             {props['Molecular_Formula']}")
+
+    print("\n[Size & Weight]")
+    print(f"  Molecular Weight:    {props['MW']:.2f}")
+    print(f"  Exact MW:            {props['ExactMW']:.4f}")
+    print(f"  Heavy Atoms:         {props['Heavy_Atoms']}")
+    print(f"  Heteroatoms:         {props['Heteroatoms']}")
+
+    print("\n[Lipophilicity]")
+    print(f"  LogP:                {props['LogP']:.2f}")
+    print(f"  Molar Refractivity:  {props['MR']:.2f}")
+
+    print("\n[Polarity]")
+    print(f"  TPSA:                {props['TPSA']:.2f}")
+    print(f"  Labute ASA:          {props['LabuteASA']:.2f}")
+    print(f"  H-bond Donors:       {props['HBD']}")
+    print(f"  H-bond Acceptors:    {props['HBA']}")
+
+    print("\n[Ring Systems]")
+    print(f"  Total Rings:         {props['Rings']}")
+    print(f"  Aromatic Rings:      {props['Aromatic_Rings']}")
+    print(f"  Saturated Rings:     {props['Saturated_Rings']}")
+    print(f"  Aliphatic Rings:     {props['Aliphatic_Rings']}")
+    print(f"  Aromatic Heterocycles: {props['Aromatic_Heterocycles']}")
+
+    print("\n[Flexibility & Complexity]")
+    print(f"  Rotatable Bonds:     {props['Rotatable_Bonds']}")
+    print(f"  Fraction Csp3:       {props['Fraction_Csp3']:.3f}")
+    print(f"  Bertz Complexity:    {props['BertzCT']:.1f}")
+
+    print("\n[Drug-likeness]")
+    print(f"  QED Score:           {props['QED']:.3f}")
+    print(f"  Lipinski Pass:       {'Yes' if props['Lipinski_Pass'] else 'No'}")
+    print(f"  Lead-like:           {'Yes' if props['Lead-like'] else 'No'}")
+    print("="*60)
+
+
+def main():
+    parser = argparse.ArgumentParser(
+        description='Calculate molecular properties for molecules',
+        formatter_class=argparse.RawDescriptionHelpFormatter,
+        epilog="""
+Examples:
+  # Single molecule
+  python molecular_properties.py "CCO"
+
+  # From file
+  python molecular_properties.py --file molecules.smi
+
+  # Save to CSV
+  python molecular_properties.py --file molecules.sdf --output properties.csv
+        """
+    )
+
+    parser.add_argument('smiles', nargs='?', help='SMILES string to analyze')
+    parser.add_argument('--file', '-f', help='Input file (SDF or SMILES)')
+    parser.add_argument('--output', '-o', help='Output CSV file')
+
+    args = parser.parse_args()
+
+    if not args.smiles and not args.file:
+        parser.print_help()
+        sys.exit(1)
+
+    if args.smiles:
+        # Process single molecule
+        props = process_single_molecule(args.smiles)
+        if props:
+            print_properties(props)
+    elif args.file:
+        # Process file
+        process_file(args.file, args.output)
+
+
+if __name__ == '__main__':
+    main()

package/bin/skills/rdkit/scripts/similarity_search.py

@@ -0,0 +1,297 @@
+#!/usr/bin/env python3
+"""
+Molecular Similarity Search
+
+Perform fingerprint-based similarity screening against a database of molecules.
+Supports multiple fingerprint types and similarity metrics.
+
+Usage:
+    python similarity_search.py "CCO" database.smi --threshold 0.7
+    python similarity_search.py query.smi database.sdf --method morgan --output hits.csv
+"""
+
+import argparse
+import sys
+from pathlib import Path
+
+try:
+    from rdkit import Chem
+    from rdkit.Chem import AllChem, MACCSkeys, rdFingerprintGenerator
+    from rdkit import DataStructs
+except ImportError:
+    print("Error: RDKit not installed. Install with: conda install -c conda-forge rdkit")
+    sys.exit(1)
+
+
+FINGERPRINT_METHODS = {
+    'morgan': 'Morgan fingerprint (ECFP-like)',
+    'rdkit': 'RDKit topological fingerprint',
+    'maccs': 'MACCS structural keys',
+    'atompair': 'Atom pair fingerprint',
+    'torsion': 'Topological torsion fingerprint'
+}
+
+
+def generate_fingerprint(mol, method='morgan', radius=2, n_bits=2048):
+    """Generate molecular fingerprint based on specified method."""
+    if mol is None:
+        return None
+
+    method = method.lower()
+
+    if method == 'morgan':
+        gen = rdFingerprintGenerator.GetMorganGenerator(radius=radius, fpSize=n_bits)
+        return gen.GetFingerprint(mol)
+    elif method == 'rdkit':
+        gen = rdFingerprintGenerator.GetRDKitFPGenerator(maxPath=7, fpSize=n_bits)
+        return gen.GetFingerprint(mol)
+    elif method == 'maccs':
+        return MACCSkeys.GenMACCSKeys(mol)
+    elif method == 'atompair':
+        gen = rdFingerprintGenerator.GetAtomPairGenerator(fpSize=n_bits)
+        return gen.GetFingerprint(mol)
+    elif method == 'torsion':
+        gen = rdFingerprintGenerator.GetTopologicalTorsionGenerator(fpSize=n_bits)
+        return gen.GetFingerprint(mol)
+    else:
+        raise ValueError(f"Unknown fingerprint method: {method}")
+
+
+def load_molecules(file_path):
+    """Load molecules from file."""
+    path = Path(file_path)
+
+    if not path.exists():
+        print(f"Error: File not found: {file_path}")
+        return []
+
+    molecules = []
+
+    if path.suffix.lower() in ['.sdf', '.mol']:
+        suppl = Chem.SDMolSupplier(str(path))
+    elif path.suffix.lower() in ['.smi', '.smiles', '.txt']:
+        suppl = Chem.SmilesMolSupplier(str(path), titleLine=False)
+    else:
+        print(f"Error: Unsupported file format: {path.suffix}")
+        return []
+
+    for idx, mol in enumerate(suppl):
+        if mol is None:
+            print(f"Warning: Failed to parse molecule {idx+1}")
+            continue
+
+        # Try to get molecule name
+        name = mol.GetProp('_Name') if mol.HasProp('_Name') else f"Mol_{idx+1}"
+        smiles = Chem.MolToSmiles(mol)
+
+        molecules.append({
+            'index': idx + 1,
+            'name': name,
+            'smiles': smiles,
+            'mol': mol
+        })
+
+    return molecules
+
+
+def similarity_search(query_mol, database, method='morgan', threshold=0.7,
+                     radius=2, n_bits=2048, metric='tanimoto'):
+    """
+    Perform similarity search.
+
+    Args:
+        query_mol: Query molecule (RDKit Mol object)
+        database: List of database molecules
+        method: Fingerprint method
+        threshold: Similarity threshold (0-1)
+        radius: Morgan fingerprint radius
+        n_bits: Fingerprint size
+        metric: Similarity metric (tanimoto, dice, cosine)
+
+    Returns:
+        List of hits with similarity scores
+    """
+    if query_mol is None:
+        print("Error: Invalid query molecule")
+        return []
+
+    # Generate query fingerprint
+    query_fp = generate_fingerprint(query_mol, method, radius, n_bits)
+    if query_fp is None:
+        print("Error: Failed to generate query fingerprint")
+        return []
+
+    # Choose similarity function
+    if metric.lower() == 'tanimoto':
+        sim_func = DataStructs.TanimotoSimilarity
+    elif metric.lower() == 'dice':
+        sim_func = DataStructs.DiceSimilarity
+    elif metric.lower() == 'cosine':
+        sim_func = DataStructs.CosineSimilarity
+    else:
+        raise ValueError(f"Unknown similarity metric: {metric}")
+
+    # Search database
+    hits = []
+    for db_entry in database:
+        db_fp = generate_fingerprint(db_entry['mol'], method, radius, n_bits)
+        if db_fp is None:
+            continue
+
+        similarity = sim_func(query_fp, db_fp)
+
+        if similarity >= threshold:
+            hits.append({
+                'index': db_entry['index'],
+                'name': db_entry['name'],
+                'smiles': db_entry['smiles'],
+                'similarity': similarity
+            })
+
+    # Sort by similarity (descending)
+    hits.sort(key=lambda x: x['similarity'], reverse=True)
+
+    return hits
+
+
+def write_results(hits, output_file):
+    """Write results to CSV file."""
+    import csv
+
+    with open(output_file, 'w', newline='') as f:
+        fieldnames = ['Rank', 'Index', 'Name', 'SMILES', 'Similarity']
+        writer = csv.DictWriter(f, fieldnames=fieldnames)
+        writer.writeheader()
+
+        for rank, hit in enumerate(hits, 1):
+            writer.writerow({
+                'Rank': rank,
+                'Index': hit['index'],
+                'Name': hit['name'],
+                'SMILES': hit['smiles'],
+                'Similarity': f"{hit['similarity']:.4f}"
+            })
+
+
+def print_results(hits, max_display=20):
+    """Print results to console."""
+    if not hits:
+        print("\nNo hits found above threshold")
+        return
+
+    print(f"\nFound {len(hits)} similar molecules:")
+    print("="*80)
+    print(f"{'Rank':<6} {'Index':<8} {'Similarity':<12} {'Name':<20} {'SMILES'}")
+    print("-"*80)
+
+    for rank, hit in enumerate(hits[:max_display], 1):
+        name = hit['name'][:18] + '..' if len(hit['name']) > 20 else hit['name']
+        smiles = hit['smiles'][:40] + '...' if len(hit['smiles']) > 43 else hit['smiles']
+        print(f"{rank:<6} {hit['index']:<8} {hit['similarity']:<12.4f} {name:<20} {smiles}")
+
+    if len(hits) > max_display:
+        print(f"\n... and {len(hits) - max_display} more")
+
+    print("="*80)
+
+
+def main():
+    parser = argparse.ArgumentParser(
+        description='Molecular similarity search using fingerprints',
+        formatter_class=argparse.RawDescriptionHelpFormatter,
+        epilog=f"""
+Available fingerprint methods:
+{chr(10).join(f'  {k:12s} - {v}' for k, v in FINGERPRINT_METHODS.items())}
+
+Similarity metrics:
+  tanimoto    - Tanimoto coefficient (default)
+  dice        - Dice coefficient
+  cosine      - Cosine similarity
+
+Examples:
+  # Search with SMILES query
+  python similarity_search.py "CCO" database.smi --threshold 0.7
+
+  # Use different fingerprint
+  python similarity_search.py query.smi database.sdf --method maccs
+
+  # Save results
+  python similarity_search.py "c1ccccc1" database.smi --output hits.csv
+
+  # Adjust Morgan radius
+  python similarity_search.py "CCO" database.smi --method morgan --radius 3
+        """
+    )
+
+    parser.add_argument('query', help='Query SMILES or file')
+    parser.add_argument('database', help='Database file (SDF or SMILES)')
+    parser.add_argument('--method', '-m', default='morgan',
+                       choices=FINGERPRINT_METHODS.keys(),
+                       help='Fingerprint method (default: morgan)')
+    parser.add_argument('--threshold', '-t', type=float, default=0.7,
+                       help='Similarity threshold (default: 0.7)')
+    parser.add_argument('--radius', '-r', type=int, default=2,
+                       help='Morgan fingerprint radius (default: 2)')
+    parser.add_argument('--bits', '-b', type=int, default=2048,
+                       help='Fingerprint size (default: 2048)')
+    parser.add_argument('--metric', default='tanimoto',
+                       choices=['tanimoto', 'dice', 'cosine'],
+                       help='Similarity metric (default: tanimoto)')
+    parser.add_argument('--output', '-o', help='Output CSV file')
+    parser.add_argument('--max-display', type=int, default=20,
+                       help='Maximum hits to display (default: 20)')
+
+    args = parser.parse_args()
+
+    # Load query
+    query_path = Path(args.query)
+    if query_path.exists():
+        # Query is a file
+        query_mols = load_molecules(args.query)
+        if not query_mols:
+            print("Error: No valid molecules in query file")
+            sys.exit(1)
+        query_mol = query_mols[0]['mol']
+        query_smiles = query_mols[0]['smiles']
+    else:
+        # Query is SMILES string
+        query_mol = Chem.MolFromSmiles(args.query)
+        query_smiles = args.query
+        if query_mol is None:
+            print(f"Error: Failed to parse query SMILES: {args.query}")
+            sys.exit(1)
+
+    print(f"Query: {query_smiles}")
+    print(f"Method: {args.method}")
+    print(f"Threshold: {args.threshold}")
+    print(f"Loading database: {args.database}...")
+
+    # Load database
+    database = load_molecules(args.database)
+    if not database:
+        print("Error: No valid molecules in database")
+        sys.exit(1)
+
+    print(f"Loaded {len(database)} molecules")
+    print("Searching...")
+
+    # Perform search
+    hits = similarity_search(
+        query_mol, database,
+        method=args.method,
+        threshold=args.threshold,
+        radius=args.radius,
+        n_bits=args.bits,
+        metric=args.metric
+    )
+
+    # Output results
+    if args.output:
+        write_results(hits, args.output)
+        print(f"\nResults written to: {args.output}")
+
+    print_results(hits, args.max_display)
+
+
+if __name__ == '__main__':
+    main()