CovPDB

CovPDB provides high-resolution cocrystal structures of biologically relevant covalent protein–ligand (cP-L) complexes to support the rational design and discovery of targeted covalent inhibitors (TCIs).

Key Features:

• Curation source: Curated from the Protein Data Bank (PDB) and comprises experimentally determined cocrystal structures.
• Contents: Contains 2,294 covalent protein–ligand (cP-L) complexes involving 733 distinct proteins and 1,501 ligands.
• Ligand annotation: Annotates chemical structures of pre-reactive electrophilic ligands.
• Reactive warheads: Annotates 93 distinct reactive warheads.
• Targetable residues: Annotates 14 types of targetable amino acid residues.
• Covalent mechanisms: Identifies 21 covalent bonding mechanisms.

Scientific Applications:

• Rational design of TCIs: Enables structure-guided design and optimization of targeted covalent inhibitors using cocrystal data.
• Warhead selection and reactivity analysis: Supports selection and comparison of pre-reactive electrophilic ligands and 93 reactive warheads for reactivity and selectivity assessments.
• Residue targeting and selectivity profiling: Facilitates mapping of 14 targetable residue types to evaluate residue-specific selectivity.
• Mechanistic interpretation: Supports interpretation of 21 identified covalent bonding mechanisms in structure–activity studies.
• Covalent interactome mapping: Enables comparative analyses across 733 proteins to explore covalent ligand selectivity and target space.

Methodology:

Curated cP-L complexes from the Protein Data Bank and annotated chemical structures of pre-reactive electrophilic ligands, reactive warheads (93), targetable residues (14), and covalent bonding mechanisms (21).