Molecular Dynamics Studies of the Protein鈥揚rotein Interactions in Inhibitor of 魏B Kinase-尾

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• 作者：Michael R. Jones ; Cong Liu ; Angela K. Wilson
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2014
• 出版时间：February 24, 2014
• 年：2014
• 卷：54
• 期：2
• 页码：562-572
• 全文大小：607K
• 年卷期：v.54,no.2(February 24, 2014)
• ISSN：1549-960X

文摘

Activation of the inhibitor of 魏B kinase subunit 尾 (IKK尾) oligomer initiates a cascade that results in the translocation of transcription factors involved in mediating immune responses. Dimerization of IKK尾 is required for its activation. Coarse-grained and atomistic molecular dynamics simulations were used to investigate the conformation鈥揳ctivity and structure鈥揳ctivity relationships within the oligomer assembly of IKK尾 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 IKK尾.