KAISO inhibition: an atomic insight.
Naveed Anjum Chikan1, Bhavaniprasad Vipperla
1a Medical Biotechnology Division, School of Bio Sciences and Technology , VIT University , Vellore 632014 , Tamilnadu , India.
Journal of Biomolecular Structure & Dynamics
|October 10, 2014
Summary
Researchers identified a promising natural compound (chem. ID 28127) as a potential anti-cancer agent. This compound targets the kaiso protein, a key player in epigenetics, showing high binding affinity and stability in simulations.
Area of Science:
- Oncology
- Epigenetics
- Computational Chemistry
Background:
- The increasing global cancer burden necessitates novel therapeutic strategies.
- Epigenetics, involving gene methylation, plays a crucial role in cancer development.
- Kaiso, a methyl-CpG binding protein, is a significant target in epigenetic cancer research.
Purpose of the Study:
- To identify novel inhibitors targeting the kaiso protein using computational methods.
- To explore the potential of natural compounds as anti-cancer agents.
- To investigate the binding interactions of potential inhibitors with the kaiso protein.
Main Methods:
- Virtual screening of a natural compound database (48,531 compounds) against the X-ray crystallographic structure of kaiso.
- Focusing on the C2H2 domain and LYS539 residue for inhibitor screening.
- Utilizing computer-aided drug design (CADD) for compound selection and molecular dynamics (MD) simulations (20 ns).
Main Results:
- Computer-aided drug design effectively filtered out unsuitable compounds.
- The top-ranked compound (chem. ID 28127) demonstrated the highest binding affinity to kaiso.
- Compound 28127 remained stable during the 20 ns molecular dynamics simulation.
Conclusions:
- Compound 28127 shows significant potential as a starting point for developing potent anti-cancer inhibitors.
- This study highlights the efficacy of CADD in identifying novel epigenetic drug candidates.
- Targeting kaiso offers a promising avenue for novel cancer therapies.
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