Structure-Based Detection of Orthosteric and Allosteric Pockets at Protein-Protein Interfaces

Protein-protein interfaces represent challenging but very promising targets to discover novel drugs with exquisite specificity profiles. We herewith chart for the first time all biologically relevant protein-protein interfaces of known X-ray structure and detect potentially druggable cavities at and nearby the interface. These cavities are then converted in simple 3D pharmacophore queries for identifying potential modulators (inhibitors, stabilizers) of druggable interfaces.