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The Role of Mass Balance and Gene Dosage in Protein Interaction Networks

  • Author(s): Oberdorf, Richard
  • Advisor(s): Kortemme, Tanja
  • et al.
Abstract

This work presents two separate investigations based on a similar theme: that the topology of

protein-protein interactions should in part be predictive of a protein's sensitivity to dosage. The

rst investigation focuses on individual multi-protein complexes examining whether protein

complex topology is a determinant of dosage sensitivity. Mass balance equations are used to

compute the response of complex formation to varying amounts of each component protein. The

computed response is then related to experimental data in the form of tness of hetezygous

deletions, overexpression phenotypes, and protein expression noise. The second investigation

focuses on larger protein interaction networks and looks specically at proteins that

interchangeably bind multiple other proteins. A series of simple networks is used to gain insight

into changes in the amount of unbound protein upon overexpression, again using equations

describing mass balance. Predictions of the simple models are then validated with experimental

data.

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