title: A comparative study of structural and conformational properties of casein kinase-1 isoforms: insights from molecular dynamics and principal component analysis.
abstract: Wnt signaling pathway regulates several developmental processes in human; however recently this pathway has been associated with development of different types of cancers. Casein kinase-1 (CK1) constitutes a family of serine-threonine protein kinase; various members of this family participate in Wnt signal transduction pathway and serve as molecular switch to this pathway. Among the known six isoforms of CK1, in human, at least three isoforms (viz. alpha, delta and epsilon) have been reported as oncogenic. The development of common therapeutics against these kinases is an arduous task; unless we have the detailed information of their tertiary structures and conformational properties. In the present work, the dynamical and conformational properties for each of three isoforms of CK1 are explored through molecular dynamics (MD) simulations. The conformational space distribution of backbone atoms is evaluated using principal component analysis of MD data, which are further validated on the basis of potential energy surface. Based on these analytics, it is suggested that conformational subspace shifts upon binding to ligands and guides the kinase action of CK1 isoforms. Further, this paper as a first effort to concurrently study all the three isoforms of CK1 provides structural basis for development of common anticancer therapeutics against three isoforms of CK1.
authors: Center of Bioinformatics, University of Allahabad, Allahabad 211002, India. Electronic address: suryabioinfo@gmail.com.
authors: Surya Pratap
authors: SP
authors: Singh
authors: Department of Biochemistry, University of Allahabad, Allahabad 211002, India. Electronic address: dwijenkumar@gmail.com.
authors: Dwijendra K
authors: DK
authors: Gupta
mesh_terms: D000595:Amino Acid Sequence; D047389:Casein Kinase I / Q000737:chemistry*; D020134:Catalytic Domain; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007527:Isoenzymes / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D025341:Principal Component Analysis; D017433:Protein Structure, Secondary; D013997:Time Factors
chemical_list: D007527:Isoenzymes; D047389:Casein Kinase I
keywords: Conformational subspaces; Molecular dynamics simulation; Principal component analysis; Wnt signaling pathway