GPCR Decoy Database (GDD)

GPCR Decoy Database (GDD) provides a curated set of decoy molecules paired with the GPCR Ligand Library (GLL) to improve computational docking and virtual screening for G protein-coupled receptors by matching physical properties while maintaining structural dissimilarity.

Key Features:

• Extensive Coverage: The GPCR Ligand Library (GLL) comprises ligands for 147 distinct GPCR targets.
• Decoy Generation: For each ligand, 39 decoy molecules were curated from the ZINC database.
• Property Matching: Decoys are selected to be physically similar to ligands across six properties: molecular weight, formal charge, hydrogen bond donors, hydrogen bond acceptors, rotatable bonds, and logP.
• Structural Dissimilarity: Decoys maintain chemical/structural dissimilarity to their paired ligands despite property matching.
• Performance Evaluation: The database was empirically assessed across 19 GPCRs and showed a reduction in enrichment scores versus bias-uncorrected decoy sets.

Scientific Applications:

• Drug Discovery: Provides matched decoys to improve discrimination between true ligands and false positives in high-throughput virtual screening.
• Structural Biology: Supports validation of ligand–receptor interaction models through controlled docking experiments.
• Medicinal Chemistry: Aids structure-based design by supplying decoys that test specificity of predicted binding interactions.

Methodology:

Decoys were drawn from the ZINC database and selected to match ligands on six physical properties (molecular weight, formal charge, hydrogen bond donors, hydrogen bond acceptors, rotatable bonds, logP) while preserving structural dissimilarity.