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This part of web site is devoted to methodological studies. We try to tell here about approaches which is used of modeling of metabolic systems and analysis of different types of bioologicla information. It is significant to mark that systems biology is dynamically upcoming discipline and research methods in this field is constantly widen and modified. However some of the methods could be considered as fundumentals of systems biology. One of such basic approaches is a modeling of biochemical systems. This methadological area is an our main scientific instrument. It could be noted that we have appreciably modified and improved these techniques.



Basic approaches of metabolic modeling

At present time it is possible to mark out three main approaches to biochemical pathways modeling: structural, stoichiometric and kinetic. Each of this approaches is developed for specific task and has several distinctions.

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Strategy of kinetic modeling of large-scale biochemical systems

Under words “kinetic modeling” we will imply the system of mechanistic ordinary differential equations, which defines state of concerned system of chemical reaction in the every time point, i.e. assign the metabolites concentration changing as time function. These equations are written down by following way

dX/dt = Vproduction X – Vconsumption X

and named equations of chemical kinetic. Here X - any metabolites concentration, Vproduction X and Vconsumption X – total rates of its production and consumption.

Kinetic model of metabolic or signal conductive pathway development involves several stages:

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Main principles of a development of individual enzymes kinetic models

Meth_enz_3One of the main steps of kinetic modeling of biochemical pathways is a development of kinetic models of individual enzymes, consisting in derivation of rate equations and verification of parameters using available experimental data.  Exactly during this step of modeling metabolic regulation of biochemical pathway is taken into account at the expense of rate equations modification and bringing into them additional expressions describing enzyme activation or inhibition.

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Main principles of a development of genetic regulation kinetic models

Meth_gene_7As a rule we take into account genetic regulation of biochemical pathways using analogous method to mathematical description of enzyme functioning. It also has same stages as such one for models of biochemical pathways. There is only one main difference. For mathematical description of genetic regulation we assign only two levels of specification – reduced and detail. In this material we show main steps of a development of the reduced description by example of transcription regulation.

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ISBSPb experience in the different modeling techniques

In the framework of systems biology a lot of different modeling methods have been developed. All these methods allow to take into model account both description of different processes functioning at all levels of biological systems organization and simulation of various types of experimental and clinical data . Based on these statements existent models could be divided into following categories. In the Institute for Systems Biology SPb we have an experience in all of these modeling techniques. Furthermore, part of these methods is our innovation (e. g. systemic models of transfer systems of organism – blood circulation, lymphatic and digestive systems).

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