Src homology 2 (SH2) domains are 100 amino acid modular units, which recognize and bind to tyrosyl-phosphorylated peptide sequences on their target proteins, and thereby mediate intracellular protein-protein interactions.
Currently, more than 50 crystallographic complexes obtained for various small-molecule SH2 domain inhibitors are available within PDB databank. The 4-centered pharmacophore model was constructed based on the selected X-Ray data (2WKM, 3GQL and 4AOI). The reference compounds were then docked into the constructed model starting form 2D structures without any stereo assignment. The obtained results are well correlated with the RSA data used (av. RMSD=0.2).
All the compounds from SH2 domains library were evaluated using the developed pharmacophore model. High-score molecules were included in the library (more than 50% of the total amount).