SBMLsqueezer version 1.2

New Features

SBMLsqueezer now automatically checks for updates. If a newer version of SBMLsqueezer is available online, the user is notified by a message window in the bottom right corner of the screen. Furthermore, the release notes of the most recent SBMLsqueezer version are shown to the user by clicking on “show release notes.”

In contrast to previous versions, SBMLsqueezer now indicates if a model already contains rate equations for all reactions or no reactions at all. In earlier versions, SBMLsqueezer did not overwrite existing kinetic equations and did also not state why. SBMLsqueezer's complete internal data structure was improved: It has become much more efficient and more straightforward.

Improved Adaptation of SBMLsqueezer to CellDesigner 4.0.1

Due to the changes in CellDesigner, SBMLsqueezer only offered zeroth order mass action kinetics as the available option to model transcription and translation processes. The reason for this was that the arrows for transcriptional/translational activation disappeared. These effects have now to be covered by a trigger and physical stimulation. Unfortunately, CellDesigner maps the old arrows for transcriptional/translational activation to catalysis instead of “trigger.” Therefore, we also have to cover the case of having a transcription or translation “catalyzed” by some stimulator. This has now been implemented and SBMLsqueezer, therefore, offers several kinetic rate equations for both processes. The same holds true for the “batch” mode of SBMLsqueezer: besides transcriptional/translational activators also all kinds of catalysts and activators/inhibitors are accepted for the Hill equation.

We now apply the inhibition pre-factor from convenience kinetics also to reversible Michaelis-Menten kinetics with multiple inhibitors. In cases where the formulas of Michaelis-Menten and convenience kinetics are equal, only one of both is offered to the user:

• For reversible or irreversible uni-uni reactions without inhibition or activation only the Michaelis-Menten equation is selectable and
• in the case of reversible uni-uni reactions with multiple inhibitors, only convenience kinetics can be applied.
• However, if the stoichiometric matrix of the reaction system does not have a full column rank, the thermodynamically independent form of the convenience kinetics can be selected as an alternative to the Michaelis-Menten equation.

Additionally, the activation pre-factor is now also applied for the mixed-type inhibition of irreversible enzymes by mutually exclusive inhibitors (SBO:0000275) if activators are assigned to the reaction.

The new SBGN representation of transcription and translation uses the trigger symbol (for the gene or the RNA molecule, depending on the process) and a reaction from some source to RNA or from some source to a protein. SBMLsqueezer did in these cases not suggest the Hill equation as a possible rate law because it still required the translation/transcription arrows that are going to be deprecated. Since this version, SBMLsqueezer also produces the identical form of the Hill equation for the old style of transcription/translation reaction and the new SBGN compliant form.

Bug Fixes

Local parameters could not be removed entirely if not necessary (this happened only in SBMLsqueezer version 1.1 because SBMLsqueezer version 1.0 did not create or delete local parameters at all).
In Michaelis-Menten-kinetics activators were multiplied incorrectly (only in the preview, not in the equation itself).

The help browser could not be started in SBMLsqueezer version 1.1 because of a null pointer exception (an image could not be loaded correctly).

Problems of the “batch mode”:

• In some cases, SBMLsqueezer did not show the correct SBO numbers (for “Hill equation” and “Henri-Michaelis-Menten equation”).
• In the kinetics summary table, SBMLsqueezer did not list the kG parameters of the thermodynamically independent convenience kinetics in the column “parameters”.
• Sometimes there was a problem with the equation preview.