title: KAISO inhibition: an atomic insight.
abstract: In today's world, the pursuit of a novel anti-cancer agent remains top priority because of the fact that the global burden of this malady is continuously increasing. Our work is no different from others in searching for new therapeutic solutions. To achieve this, we are looking into Epigenetics, the phenomenon governed by hypermethylation and hypomethylation of tumor suppressor genes and oncogenes, respectively. Our target for this study is an important intermediary methyl-CpG binding protein named kaiso. In our study, we have used the X-ray crystallographic structure of Kaiso for virtual screening and molecular dynamics simulations to study the binding modes of possible inhibitors. The C2H2 domain comprising LYS539 was used for screening the inter bio screen Database having 48,531 natural compounds. Our approach of using computer-aided drug designing methods helped us to remove the execrable compounds and narrowed our focus on a selected few for molecular simulation studies. The top ranked compound (chem. ID 28127) exhibited the highest binding affinity and was also found to be stable throughout the 20 ns timeframe. This compound is therefore a good starting point for developing strong inhibitors.
authors.affiliation: a Medical Biotechnology Division, School of Bio Sciences and Technology , VIT University , Vellore 632014 , Tamilnadu , India.
authors.forename: Naveed Anjum
authors.initials: NA
authors.lastname: Chikan
authors.forename: Bhavaniprasad
authors.initials: B
authors.lastname: Vipperla
mesh_terms: D001665:Binding Sites; D016000:Cluster Analysis; D017076:Computer-Aided Design; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D008024:Ligands; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: Kaiso; drug designing; free energy landscape; molecular docking; molecular dynamics simulations