DrugDomain 2.0

DrugDomain 2.0 catalogs domain-ligand interactions across the entire Protein Data Bank by linking Evolutionary Classification Of protein Domains (ECOD) classifications to ligand binding events, and extends annotations to human drug targets lacking experimental structures using AlphaFold predictions.

Key Features:

• Domain-Ligand Interaction Mapping: Links ECOD evolutionary domain classifications to ligand binding events across the entire Protein Data Bank.
• AI-Driven Structure Prediction Integration: Leverages AlphaFold predictions to extend domain-ligand annotations to human drug targets lacking experimental structures.
• Comprehensive Ligand Coverage: Catalogs interactions with over 37,000 PDB ligands and 7,560 DrugBank molecules.
• Post-Translational Modification Integration: Integrates more than 6,000 small-molecule-associated post-translational modifications.
• PTM-Modified Protein Models: Provides context for 14,000+ PTM-modified human protein models featuring docked ligands.
• Proteome and Structural Coverage: Encompasses 43,023 unique UniProt accessions and 174,545 PDB structures.

Scientific Applications:

• Drug Target Relationship Analysis: Provides insights into drug target relationships through systematic mapping of domain-ligand interactions at the structural level.
• Remote Homolog Detection: Enables detection of remote homologs across proteomes through ECOD's hierarchy built around distant evolutionary relationships.
• Human Drug Target Annotation: Extends structural annotations to human drug targets that lack experimental three-dimensional structures.
• Post-Translational Modification Study: Supports investigation of small-molecule-associated post-translational modifications and their structural contexts.

Methodology:

DrugDomain 2.0 links Evolutionary Classification Of protein Domains (ECOD) classifications to ligand binding events across the entire Protein Data Bank, and leverages AlphaFold predictions to extend domain-ligand annotations to human drug targets lacking experimental structures.