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Dynamic conformational ensembles regulate casein kinase-1 isoforms: Insights from molecular dynamics and molecular docking studies
Affiliation:1. Center of Bioinformatics (IIDS), University of Allahabad, Allahabad 211002, India;2. Department of Biochemistry, University of Allahabad, Allahabad 211002, India;1. Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education, Jilin University, ChangChun 130012, PR China;2. School of Life Science, Jilin University, ChangChun 130012, PR China;1. National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Kochi 16, Kerala, India;2. CSIR – National Institute of Oceanography, Regional Centre, Kochi 18, Kerala, India;3. Bioinformatics Facility, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 14, Kerala, India;4. Department of Marine Biology, Microbiology and Biochemistry, Cochin University of Science and Technology, Kochi 16, Kerala, India;1. Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544-5263, USA;2. Program in Applied and Computational Mathematics, Princeton University, Princeton, NJ 08544-1000, USA;3. Andlinger Center for Energy and the Environment, Princeton University, Princeton, NJ 08544-5263, USA;1. Applied Science College, Harbin University of Science and Technology, Harbin 150080, China;2. School of Materials Science and Engineering, Harbin University of Science and Technology, Harbin 150040, China;3. Department of the Applied Chemistry, Harbin Institute of Technology, Harbin 150001, China
Abstract:Casein kinase-1 (CK1) isoforms actively participate in the down-regulation of canonical Wnt signaling pathway; however recent studies have shown their active roles in oncogenesis of various tissues through this pathway. Functional loss of two isoforms (CK1-α/ε) has been shown to activate the carcinogenic pathway which involves the stabilization of of cytoplasmic β-catenin. Development of anticancer therapeutics is very laborious task and depends upon the structural and conformational details of the target. This study focuses on, how the structural dynamics and conformational changes of two CK1 isoforms are synchronized in carcinogenic pathway. The conformational dynamics in kinases is the responsible for their action as has been supported by the molecular docking experiments.
Keywords:Wnt signaling pathway  Molecular dynamics simulation  Principal component analysis
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