PPI

PPI identifies druggable cavities at protein–protein interfaces from known 3D structures to prioritize pockets for rational ligand design to stabilize or disrupt specific PPIs.

Key Features:

• Automated Structure-Based Workflow: It uses a fully automated, structure-based workflow to identify and prioritize druggable cavities at protein–protein interfaces, enabling application across entire interactomes.
• Extensive Database (Protein Data Bank): Applied to the Protein Data Bank, it identified and classified 164,514 druggable cavities into four groups: interfacial, rim, allosteric, and orthosteric.
• Unique Property Space of PPI Cavities: Systematic comparison shows PPI cavities occupy a distinct property space compared with conventional druggable pockets, indicating traditional compound libraries may not effectively target the most druggable PPI cavities.

Scientific Applications:

• Small-molecule PPI modulation: Prioritizes druggable cavities to support rational design of small molecules that stabilize or disrupt specific protein–protein interactions relevant to complex diseases.

Methodology:

Automated structure-based analysis of known 3D PPI structures that systematically identifies druggable sites and classifies them based on characteristics and spatial orientation relative to the protein interface.