2022 Science Advances Paper
Note:
The following examples simulate figures from the 2022 Science Advances paper (Schaffter and Strychalski), Cotranscriptionally encoded RNA strand displacement circuits. See the paper for a detailed description of each experiment and/or simulation.
In that paper a relatively weak output toehold was used with domain 2 for reportering. So in the following scripts, gates with output domain 2 have their reverse strand displacement rate constant decreased compared to the default in molecular_species().
Figure 2D
Figure 2D simulates a basic, one-layer ctRSD circuit with different input template concentrations.
- Useful Features:
changing indiviudal rate constants within molecular_species()
Figure 4C
Figure 4C simulates a ctRSD OR element.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
Figure 4F
Figure 4F simulates a ctRSD AND gate.
- Useful Features:
Specifying AND gates within molecular_species()
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
Figure 4H
Figure 4H uses fuel reactions to simulate a signal amplification element.
- Useful Features:
Specifying fuel strands within molecular_species()
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
Figure 5B
Figure 5B simulates a one, two, three, and four layer ctRSD cascades.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
Figure 5C
Figure 5C simulates a 4-input ctRSD OR element.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
Figure 5D
Figure 5D simulates a two layer cascade of ctRSD AND gates.
- Useful Features:
Specifying AND gates within molecular_species()
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
Figure 5E
Figure 5E simulates a two layer cascade of a ctRSD OR gate leading to a ctRSD AND gate.
- Useful Features:
Specifying AND gates within molecular_species()
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
Warning!
The original implementation of the model in ctRSD-simulator-1.0.1 overestimated the reverse rates for FAN-IN circuts. The new model implementation in ctRSD-simulator-2.0 corrected this issue. Therefore, the results can be slightly different between simulators.
More information on the imporved model implementation can be found here.
Figure 5F
Figure 5F simulates a two layer cascade of a ctRSD AND gate leading to a ctRSD OR element.
- Useful Features:
Specifying AND gates within molecular_species()
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
SI Figure 12
SI Figure 12 simulates an experiment conducted to estimate ribozyme cleavage rate. In the experiment, G{1,2} is initially transcribed for 15 min by itself and given different krz values. After 15 min, the G{1,2} template is degraded (concentration set to 0) and the fraction of the cleaved gate as a function of time is observed in the absence of transcription.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
Plotting species other than S{}
Discontinuous simulation feature in simulate()
SI Figure 16
SI Figure 16 simulates mixing fixed concentations of I{1} and G{1,2} with a DNA reporter.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
changing indiviudal initial conditions within molecular_species()
Discontinuous simulation feature in simulate()
SI Figure 18
SI Figure 18 simulates potential mechanims for uncleaved gates reacting slowly with inputs.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
SI Figure 19
Figure 19 simulates the effect of increase reversing rates on one, two, three, and four layer cascades.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
SI Figure 26
Figure 26 simulates steric hindrance between the leak products and ctRSD gates could reduce overall leak observed in longer cascades.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
SI Figure 27B
Figure 27B simulates lowering the forward strand displacement rate constant for I{4}.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
SI Figure 30C
Figure 30C simulates how ctRSD circuit kinetics depend on toehold length and the length of a single-stranded spacer after the self-cleaving ribozyme.
- Useful Features:
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()
SI Figure 31B
Figure 31B in the SI shows the influence of total template concentration and T7 RNAP concentration on transcriptional load. In terms, of the simulator, this example presents the need to be able to test different transcription rates to find the best rate for a set of data. The simulator uses transcription_calibration for this purpose.
Note:
Click here for full features of the transcription_calibration() function.
- Useful Features:
calibration transcription rates using transcription_calibration()
globally changing rate constants with global_rate_constants()
changing indiviudal rate constants within molecular_species()