Pharmacophore Modeling

A pharmacophore defines the minimum set of 3D chemical features — their types, spatial arrangement, and tolerance spheres — required for biological activity. Used for scaffold hopping, virtual screening, and SAR hypothesis generation.

When to Use This Skill

• Derive pharmacophore from a co-crystal structure (structure-based)
• Extract common features from a set of active ligands (ligand-based)
• Screen a compound library for pharmacophore matches (VS)
• Compute pharmacophore fingerprints for similarity searching
• Identify scaffold-hopping opportunities (2D-diverse but 3D-similar)
• Validate binding mode hypotheses against active/inactive SAR data

Feature Types

Quick Start

from rdkit import Chem
from rdkit.Chem import AllChem, MolStandardize
from rdkit.Chem.Pharm3D import Pharmacophore, EmbedLib
from rdkit.Chem import rdMolChemicalFeatures

# Load feature factory (FDEF file bundled with RDKit)
import os
from rdkit import RDConfig
fdefName = os.path.join(RDConfig.RDDataDir, 'BaseFeatures.fdef')
factory = rdMolChemicalFeatures.BuildFeatureFactory(fdefName)

# Get features from a molecule
mol = Chem.MolFromSmiles('c1ccc(cc1)C(=O)O')  # benzoic acid
feats = factory.GetFeaturesForMol(mol)
for feat in feats:
    print(f"{feat.GetFamily():12s} {feat.GetType():20s} atoms={list(feat.GetAtomIds())}")

Router — What to Read

Software

Related Skills

• rdkit — conformer generation, substructure, 2D fingerprints
• docking — binding poses used to derive structure-based pharmacophore
• mdanalysis — dynamic pharmacophore from MD trajectories
• daylight-theory — SMARTS syntax for custom feature FDEF files