Forkhead box (Fox) proteins are a superfamily of evolutionarily conserved transcriptional regulators, which
control a wide spectrum of biological processes. FoxG1 is a transcriptional repressor, whose function has been elucidated
recently. FoxG1 overexpression was found to be associated with medulloblastoma and hepatoblastoma. It was suggested
that the inhibition of FoxG1 could be a potential target for the development of molecular therapeutics in such type of cancers.
Since, experimentally derived structure for FoxG1 is unavailable in any of the structural databases, modeling of the
DNA binding domain of this protein was carried out. Potential binding sites on the protein surface were predicted. Pharmacophoric
features were derived from the binding site that lies near the protein-DNA binding interface and this pharmacophore
was employed for virtual screening of compounds. To the best of our knowledge, this is the first pharmacophore
model proposed for screening inhibitors of FoxG1, which may interfere with its transcriptional repressor functionality.
The interactions of the binding site residues with the top scoring ligand hits were analyzed. These ligands may be used for
the development of potential inhibitors of FoxG1 protein.
Keywords: FoxG1, Metastasis, Homology modeling, Pharmacophore, Docking, Virtual Screening
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