Computational protocol: Modeling of the Bacterial Mechanism of Methicillin-Resistance by a Systems Biology Approach

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Protocol publication

[…] To develop models of integrated biochemical levels, it is necessary to consider the mechanisms by which biochemical information transfer occurs. The network of genes, mRNA, proteins and metabolites was created using CellDesigner version 4.0 (, a software that enables users to describe molecular interactions using a well-defined and consistent graphical notation . The data of molecular interactions are stored in Systems Biology Markup Language (SBML; . Since SBML is a standard machine-readable model representation format, all the information can be used for a range of computational analysis, including computer simulation .To simulate the dynamic behavior of these biochemical networks, kinetic equations have to be associated with each reaction. The software SBMLsqueezer was used to generate kinetic rate equations for our biochemical network. This approach facilitates the modeling steps via automated generation of equation and overcomes the highly error-prone and cumbersome process of manually assigning kinetic equations. For each reaction the kinetic equation is derived from the stoichiometry, the participating species (e.g., proteins, mRNA or generic molecules) as well as the regulatory relations (activation, inhibition or other modulations) of the SBGN diagram. The software SBMLsqueezer offers different types of kinetics (i.e. mass-action, Hill, and several Michaelis-Menten-based kinetics), each including activation, inhibition and reversibility or irreversibility for representing gene regulatory, signal transduction, protein, metabolic, and mixed networks. The rate laws were generated by considering for each reaction all participating reactants, products and regulators. In particular, for gene regulatory networks, i.e., transcriptional and translational processes, the Hill equation is applied.After invoking SBMLsqueezer, the kinetic formulas are generated and assigned to the model, which was then simulated in CellDesigner ver 4.0. Details on reaction type and differential equations are reported in , Supplementary , and and Supplementary . Moreover, the substance amount and time are expressed in number of molecules and seconds, respectively (see for details Table 3 in Hucka et al (2003) ). […]

Pipeline specifications

Software tools CellDesigner, SBMLsqueezer
Application Mathematical modeling
Chemicals Methicillin