Discrete event, multi-level simulation of metabolite channeling

Alteration of mitochondrial protein complexes in relation to metabolic regulation under short-term oxidative stress in Arabidopsis seedlings

“…Enzyme proteins can form multienzyme protein complexes that serve to microcompartment metabolic pathways and thus allow operation of more efficient metabolic transitions (Saks et al, 2008). The organisation of metabolic pathways by enzyme protein complexes has been discussed as the main molecular-scale organisation units to orchestrate the multiple metabolic processes (Degenring et al, 2004;Durek and Walther, 2008;Graham et al, 2007;Ro and Douglas, 2004;Srere, 2000). Additionally transient complexes offer the possibility of fast exchange of some of the polypeptide components upon reassembly and thus can be a molecular basis for rapid and fine tuning or redirection of metabolism.…”

Discrete event modelling and simulation in systems biology

“…Both approaches employ a microlevel view on the molecules in the system, instead of simply representing species populations by discrete numbers. That is, they allow a detailed, complex description of molecules, which may even contain additional structure for internal processes (eg the indole channel in the Tryptophan synthase (Degenring et al, 2004)). Here, stochasticity can be easily added to describe the behaviour of single model entities, that is, the state transitions of an atomic DEVS model or a STATECHART.…”

Discrete Event Multi-level Models for Systems Biology

“…Therefore a discrete-event stochastic multi-level model was generated [100] to allow a more detailed description of the individual enzymes including additional structural (qualitative) information about the enzymes and to allow at the same time the reproduction of the in-vitro experiments. In spite of the additional com- [29] plexity the multi-level model should remain transparent for the experimentalists, see figure 3.…”

“…in our case mainly the different binding-states of the enzymes, have to be modeled; -corresponding simulations can be realized in Stochsim: at each time step of the simulation, which is determined by the fastest reaction step, [29] i.e. in our case the tunneling reaction, two molecules were randomly chosen.…”

“…The importance of these interdependencies has been emphasized for systems in general [19] and biological systems in particular [20,21], and also recently for Systems Biology with increasing urgency [22,23,24,25] motivating the development of concrete models, e.g. [26,27,28,29]. This paper is organized as follows: in chapter two the modeling approaches in the area of Systems Biology are categorized into the three modeling dimensions, which were described above (quantitative-qualitative, continuous-discrete and stochastic-deterministic); chapter three introduces the idea of the different organization levels for the distinction of the modeling approaches (micro, macro and multi-level models) and interrelates the categorization approach to the modeling dimensions studied in chapter two with a focus on multi-level models; after theoretical considerations about the different modeling dimensions and their interdependencies, chapter four illustrates the explorations based on a biological application example; chapter five gives a more in-detail discussion of the composition and interaction of multi-level models; it is followed by a general discussion, summary and outlook.…”