title: In silico prediction of novel inhibitors of the DNA binding activity of FoxG1.
abstract: 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.
authors: School of Biotechnology National Institute of Technology Calicut - 673601, Kerala, India.
authors: Syam Bhuvanachandran
authors: SB
authors: Nair
authors: Shaik Mahammad Abdul
authors: SM
authors: Fayaz
authors: Rajanikant Golgodu
authors: RG
authors: Krishnamurthy
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology; D004247:DNA / Q000378:metabolism*; D062313:Databases, Pharmaceutical; D004353:Drug Evaluation, Preclinical; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D014584:User-Computer Interface
chemical_list: C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D004247:DNA