Bioinformatics Vol. 18 no. 1 2002
Pages 67-76
© 2002 Oxford University Press
Discrete simulation of regulatory homo- and heterodimerization in the apoptosis effector phase
1 Institute for Theoretical Chemistry and
Molecular Structural Biology, University of Vienna, Dr Bohrgasse 9,
A-1030 Vienna, Austria
2 University Clinic for Internal Medicine
III, Division of Nephrology,
Währinger
Gürtel 18–20, A-1090 Vienna,
Austria
3 Division of Nephrology, Leopold Franzens
University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria
Received on April 9, 2001
; revised on July 9, 2001
; accepted on July 13, 2001
Motivation: Quantitative simulation of molecular reaction networks is among the most promising approaches towards an understanding of complex biochemical pathways. Numerous qualitative as well as quantitative data from diverse experimental settings, in particular from genomics and proteomics, have to be contextually linked to convert static data into dynamic functionality.
Results: This paper presents the Lattice Molecular Automaton, a Cellular Automaton-based simulation tool, capable of representing complex molecular dynamics at different levels of granularity. A data structure concept represents molecular units, whose dynamics, embedded on a 2D grid, is defined via detailed intermolecular interaction profiles. The data structures hold diverse information as molecular type, potential, as well as kinetic energy states, which allows a precise representation of intracellular reaction networks. The molecular dynamics is performed via local computation of individual molecular states on the lattice, which, in conjunction with discretized space and time, enables excellent scalability of this simulation concept. This paper finally gives Lattice Molecular Automaton simulation results on key elements of apoptosis, the cell death cascade, in particular focusing on the regulatory function of homo- and heterodimerization of members of the Bcl-2 protein family in the apoptosis effector phase. The regulatory proteins Bcl2, Bax, and Bak constitute a diffusion-driven molecular switch with inherent damping of apoptosis induction, thereby controlling the apoptosis reaction cascade under noisy, external apoptosis inducing conditions.
Contact: bernd.mayer{at}univie.ac.at
* To whom correspondence should be addressed.
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