Molecular dynamics studies of the protein-protein interactions in inhibitor of κB kinase-β.
Activation of the inhibitor of κB kinase subunit β (IKKβ) oligomer initiates a cascade that results in the translocation of transcription factors involved in mediating immune responses. Dimerization of IKKβ is required for its activation. Coarse-grained and atomistic molecular dynamics simulations were used to investigate the conformation-activity and structure-activity relationships within the oligomer assembly of IKKβ that are impacted upon activation, mutation, and binding of ATP. Intermolecular interactions, free energies, and conformational changes were compared among several conformations, including a monomer, two different dimers, and the tetramer. Modifications to the activation segment induce conformational changes that disrupt dimerization and suggest that the multimeric assembly mediates a global stability for the enzyme that influences the activity of IKKβ.
Department of Chemistry and Center for Advanced Scientific Computing and Modeling, University of North Texas , Denton, Texas 76203-5017, United States.
Michael R
MR
Jones
Cong
C
Liu
Angela K
AK
Wilson
D000255:Adenosine Triphosphate / Q000378:metabolism; D004795:Enzyme Stability; D006860:Hydrogen Bonding; D051550:I-kappa B Kinase / Q000737:chemistry* / Q000378:metabolism*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
D000255:Adenosine Triphosphate; D051550:I-kappa B Kinase