This calculator explores the effects of different combinations of basal (unregulated) and regulated rate constants on transcript flux. The initiation mechanism consists of three states: free promoter (R+P), closed complex (RPc), and open complex (RPo) with reversible transitions between R+P, RPc , and RPo as is indicated in the schematic below. From open complex, the polymerase may irreversibly escape the promoter resulting in a free promoter and an mRNA transcript. The concentration of the polymerase ([R], nM) is modeled explicitly and is assumed to be constant. First, enter basal parameters for the promoter of interest in the boxes below. The flux control coefficients determined by the set of basal rate constants will be displayed (Cφ). Second, move the slider bars to set how that particular parameter will be regulated. The output will be displayed on the right in real time. Both the basal and regulated mRNA flux and the flux ratio are reported numerically. In addition, the area of the circle represents the flux ratio graphically with larger green circles indicating activation and smaller red circles indicating repression. Lastly, the relative free energy landscapes depicting the state and transition states are plotted for comparison. The prefactor (A) is constant for all transitions set and is set to 5.0*10^6 1/s and RT is 0.616 at 37C. The landscape barriers are calculated as dG = -RTln(k/A) and should only be compared qualitatively. Both the basal and regulated energy landscapes may be downloaded using the button below the plot. See Reference for more information.
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