Structure-Based Detection of Orthosteric and Allosteric Pockets at Protein–Protein Interfaces
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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.
Key wordsProtein Data Bank Interface Cavity Druggability Pharmacophore Virtual screening
This work was supported by a PhD grant from CNRS (Institut de Chimie) and the Alsace Region to FSD. We thank Prof. M. Rarey (University of Hamburg, Germany) for providing an executable version of ProToss. The High-performance Computing Center (University of Strasbourg, France) and the Calculation Center of the IN2P3 (CNRS, Villeurbanne, France) are acknowledged for allocation of computing time and excellent support.