In Silico prediction of novel inhibitors of the DNA binding activity of FoxG1

Syam Bhuvanachandran Nair, Shaik Mahammad Abdul Fayaz, Rajanikant Golgodu Krishnamurthy

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1155-1162
Number of pages8
JournalMedicinal Chemistry
Volume8
Issue number6
DOIs
Publication statusPublished - 01-11-2012

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Computer Simulation
Binding Sites
DNA-Binding Proteins
DNA
Ligands
Forkhead Transcription Factors
Hepatoblastoma
Biological Phenomena
Medulloblastoma
Membrane Proteins
Databases
Neoplasms
Proteins
Therapeutics

All Science Journal Classification (ASJC) codes

  • Drug Discovery

Cite this

Nair, Syam Bhuvanachandran ; Fayaz, Shaik Mahammad Abdul ; Krishnamurthy, Rajanikant Golgodu. / In Silico prediction of novel inhibitors of the DNA binding activity of FoxG1. In: Medicinal Chemistry. 2012 ; Vol. 8, No. 6. pp. 1155-1162.
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In Silico prediction of novel inhibitors of the DNA binding activity of FoxG1. / Nair, Syam Bhuvanachandran; Fayaz, Shaik Mahammad Abdul; Krishnamurthy, Rajanikant Golgodu.

In: Medicinal Chemistry, Vol. 8, No. 6, 01.11.2012, p. 1155-1162.

Research output: Contribution to journalArticle

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