bio-substructure-search

name	bio-substructure-search
description	Searches molecular libraries for substructure matches using SMARTS patterns with RDKit. Filters compounds by pharmacophore features, functional groups, or scaffold matches with atom mapping. Use when finding compounds containing specific chemical moieties or filtering libraries by structural features.
tool_type	python
primary_tool	RDKit

Substructure Search

Find molecules containing specific structural patterns using SMARTS.

Basic Substructure Search

from rdkit import Chem

mol = Chem.MolFromSmiles('c1ccc(O)cc1CCO')

# Check if pattern exists
pattern = Chem.MolFromSmarts('[OH]')  # Hydroxyl group
has_hydroxyl = mol.HasSubstructMatch(pattern)
print(f'Contains hydroxyl: {has_hydroxyl}')

# Get all matches (atom indices)
matches = mol.GetSubstructMatches(pattern)
print(f'Hydroxyl positions: {matches}')

Common SMARTS Patterns

Pattern	SMARTS	Description
Hydroxyl	[OH]	Alcohol/phenol
Primary amine	[NH2]	Primary amine
Secondary amine	[NH1]	Secondary amine
Carboxylic acid	[CX3](=O)[OX2H1]	COOH
Amide	[CX3](=O)[NX3]	C(=O)N
Benzene	c1ccccc1	Phenyl ring
Any aromatic	[a]	Any aromatic atom
Halogen	[F,Cl,Br,I]	Any halogen

Library Filtering

from rdkit import Chem

def filter_by_substructure(molecules, smarts, exclude=False):
    '''
    Filter molecules by substructure presence/absence.

    Args:
        molecules: List of RDKit mol objects
        smarts: SMARTS pattern string
        exclude: If True, return molecules WITHOUT the pattern
    '''
    pattern = Chem.MolFromSmarts(smarts)
    if pattern is None:
        raise ValueError(f'Invalid SMARTS: {smarts}')

    filtered = []
    for mol in molecules:
        if mol is None:
            continue
        has_match = mol.HasSubstructMatch(pattern)
        if exclude:
            if not has_match:
                filtered.append(mol)
        else:
            if has_match:
                filtered.append(mol)

    return filtered

# Filter for amines
amines = filter_by_substructure(library, '[NX3;H2,H1,H0]')

# Exclude reactive groups
clean = filter_by_substructure(library, '[N+]([O-])=O', exclude=True)  # No nitro

Multiple Pattern Filtering

def filter_multiple_patterns(molecules, include_patterns=None, exclude_patterns=None):
    '''
    Filter by multiple inclusion and exclusion patterns.
    '''
    result = list(molecules)

    if include_patterns:
        for smarts in include_patterns:
            pattern = Chem.MolFromSmarts(smarts)
            result = [m for m in result if m and m.HasSubstructMatch(pattern)]

    if exclude_patterns:
        for smarts in exclude_patterns:
            pattern = Chem.MolFromSmarts(smarts)
            result = [m for m in result if m and not m.HasSubstructMatch(pattern)]

    return result

# Find compounds with both amine and carboxylic acid (amino acids)
amino_acids = filter_multiple_patterns(
    library,
    include_patterns=['[NX3;H2]', '[CX3](=O)[OX2H1]']
)

Atom Mapping

from rdkit import Chem

def get_substructure_atoms(mol, smarts):
    '''
    Get all atoms matching a pattern with their indices.
    '''
    pattern = Chem.MolFromSmarts(smarts)
    matches = mol.GetSubstructMatches(pattern)

    results = []
    for match in matches:
        atoms = [mol.GetAtomWithIdx(i) for i in match]
        results.append({
            'indices': match,
            'symbols': [a.GetSymbol() for a in atoms]
        })

    return results

# Find and characterize all aromatic rings
mol = Chem.MolFromSmiles('c1ccc2c(c1)cccc2')
rings = get_substructure_atoms(mol, 'c1ccccc1')
print(f'Found {len(rings)} aromatic 6-membered rings')

Recursive SMARTS

# Recursive SMARTS for complex patterns

# Phenyl attached to carbonyl
pattern = '[$(c1ccccc1C(=O))]'

# Ortho-substituted phenyl
ortho_pattern = '[$(c1ccc([*])cc1[*])]'

# Electron-withdrawing group on aromatic
ewg_aromatic = '[$(c[$(C(=O)),$(C#N),$(N(=O)=O)])]'

mol = Chem.MolFromSmiles('c1ccc(C(=O)O)cc1')
pattern = Chem.MolFromSmarts('[$(c1ccccc1C(=O))]')
print(mol.HasSubstructMatch(pattern))  # True

Visualization with Highlighting

from rdkit.Chem.Draw import rdMolDraw2D

def draw_with_highlights(mol, smarts, filename):
    '''Draw molecule with substructure highlighted.'''
    pattern = Chem.MolFromSmarts(smarts)
    match = mol.GetSubstructMatch(pattern)

    if not match:
        print('No match found')
        return

    drawer = rdMolDraw2D.MolDraw2DCairo(400, 300)
    drawer.DrawMolecule(mol, highlightAtoms=match)
    drawer.FinishDrawing()

    with open(filename, 'wb') as f:
        f.write(drawer.GetDrawingText())

# Highlight carboxylic acid
draw_with_highlights(mol, '[CX3](=O)[OX2H1]', 'highlighted.png')

Related Skills

• molecular-io - Load molecules for searching
• similarity-searching - Fingerprint-based searching
• admet-prediction - Filter before ADMET analysis