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|Title:||Computational modeling of ErbB kinase oligomeric state.||Authors:||Lim, Sing Mei.||Keywords:||DRNTU::Science::Biological sciences::Biomathematics||Issue Date:||2010||Abstract:||Epidermal growth factor receptor (EGFR), a member of ErbB family, has been recently proposed to be activated allosterically through asymmetric dimerization of the kinase domain. This study aimed to first investigate whether the reported configuration of asymmetric assembly is conserved across the ErbB family protein and would there be other possible configurations that have yet to be discovered. Secondly, it is to understand the relationships between two monomers in a dimeric state. Computer modeling coupled with structural studies of crystal symmetry contacts examined the dimeric configuration of ErbB kinase domains. Integration of bioinformatics tools allows the interactions energy calculation, model optimization and domain motion study upon allosteric modulation. The results yield favourable interaction energy for asymmetric assembly across all ErbB family dimers. Besides, a novel configuration is identified and described as juxtamembrane A-C lobe configuration (JMA-C lobe) in this study; it is proposed to mediate higher order of oligomerization among EGFR kinase domains. Allosteric modulation of EGFR dimer is showed to depend on its monomer activation state and relative orientation. In all, the findings support asymmetric dimerization of EGFR kinase and proposed novel ideas to further understanding of ErbB protein mode of action and oligomerization.||URI:||http://hdl.handle.net/10356/39789||Rights:||Nanyang Technological University||Fulltext Permission:||restricted||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Student Reports (FYP/IA/PA/PI)|
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