Rule-based Computational Modeling of Modular Signaling Protein Interactions

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dc.contributor.advisor Orlin D. Velev, Committee Member en_US
dc.contributor.advisor Jason M. Haugh, Committee Chair en_US
dc.contributor.advisor Alun L. Lloyd, Committee Member en_US
dc.contributor.advisor Balaji M. Rao, Committee Member en_US Barua, Dipak en_US 2010-04-02T19:08:57Z 2010-04-02T19:08:57Z 2008-11-16 en_US
dc.identifier.other etd-08122008-144717 en_US
dc.description.abstract Intracellular signal transduction pathways are comprised of complex interactions among cellular proteins and other biomolecules. The structures of signaling proteins/enzymes are often modular, with conserved domains that carry out specific interactions or catalytic functions, and their core activities are dictated through coordinated intra- and inter-molecular interactions. In collaboration with Prof. James Faeder (Computational Biology, University of Pittsburgh), we have applied a computational algorithm for generating large networks of kinetic equations based on a much smaller set of mechanistic rules. Using this rule-based approach, we have formulated kinetic models that account for the modular domain structure of specific signaling proteins, including Shp2 (Src homology-2 domain containing protein tyrosine phosphatase 2), PI3K (phosphatidilinositol-3-kinase) regulatory subunit, and SH2-B (a Jak2 kinase activating adaptor protein). Analysis of these models reveals the combinatorial possibilities of reactions and interactions that might occur in living cells. We propose here to extend this rule-based approach for larger pathway models through systematic reduction and integration of small subsystem models. en_US
dc.rights I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dis sertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to NC State University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. en_US
dc.subject BioNetGen en_US
dc.subject Cell Signal Transduction en_US
dc.subject SH2-B en_US
dc.subject Shp2 en_US
dc.subject Protein domain en_US
dc.subject PI3K en_US
dc.subject Rule-based model en_US
dc.title Rule-based Computational Modeling of Modular Signaling Protein Interactions en_US PhD en_US dissertation en_US Chemical Engineering en_US

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