PDEStrIAn

PDEStrIAn analyzes 220 phosphodiesterase (PDE) catalytic domain crystal structures from the Protein Data Bank (PDB) to annotate PDE–ligand interactions and enable structural characterization of binding modes.

Key Features:

• Systematic Structural Alignment: Aligns 57 PDE ligand-binding site residues across structures to enable comparative analysis of binding sites and subtype-specific features.
• Interaction Fingerprint Analysis: Computes interaction fingerprints (IFPs) for PDE–ligand complexes to identify conserved and selective interaction hot spots and to classify ligand binding modes.
• Substructure Analysis with ChEMBL Integration: Performs substructure analysis of cocrystallized PDE ligands integrated with ChEMBL to support scaffold hopping and identification of recurring chemical motifs.
• Binding Requirement Insights: Systematically mines structural data to elucidate structural prerequisites for effective PDE binding that inform selective inhibitor design.

Scientific Applications:

• Drug discovery and lead optimization: Supports design and optimization of selective and potent PDE inhibitors by revealing interaction hot spots and binding modes.
• Scaffold hopping and medicinal chemistry: Facilitates scaffold hopping and identification of novel chemical scaffolds via substructure analysis and ChEMBL comparisons.
• Subtype and ligand classification: Enables classification of PDE subtypes and ligands based on aligned binding-site residues and interaction fingerprints.

Methodology:

Analysis of 220 PDE catalytic domain crystal structures from the PDB, alignment of 57 binding-site residues, computation and analysis of interaction fingerprints (IFPs), and integration of substructure analysis with ChEMBL.