Identifying dynamical bottlenecks of stochastic transitions in biochemical networks

Phys Rev Lett. 2012 Feb 3;108(5):058102. doi: 10.1103/PhysRevLett.108.058102. Epub 2012 Jan 30.

Abstract

In biochemical networks, identifying key proteins and protein-protein reactions that regulate fluctuation-driven transitions leading to pathological cellular function is an important challenge. Using large deviation theory, we develop a semianalytical method to determine how changes in protein expression and rate parameters of protein-protein reactions influence the rate of such transitions. Our formulas agree well with computationally costly direct simulations and are consistent with experiments. Our approach reveals qualitative features of key reactions that regulate stochastic transitions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Animals
  • Biochemical Phenomena / physiology*
  • Cell Physiological Phenomena*
  • Computer Simulation
  • Finite Element Analysis
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / genetics
  • Gene Expression / physiology
  • Humans
  • Kinetics
  • Models, Biological
  • Neural Networks, Computer*
  • Proteins / chemistry
  • Stochastic Processes*
  • ras Proteins / chemistry
  • ras Proteins / genetics

Substances

  • Proteins
  • GTP-Binding Proteins
  • ras Proteins