###### Figure 11. Transcription rate distribution of 6 different composite promoters, and the relationship between transcription rate and concentration of lactate, fixing oxygen concentration at 0 and 0.2.
@@ -533,17 +539,24 @@ We changed the parameter $F_{loop}$ according to Table 3, and simulated the tran
According to the distance between the FNR protein binding site and the RNA polymerase binding site, the binding of the two proteins adopts different molecular mechanisms (Figure 8). When the two binding sites are 26.5 bases apart, only the C-terminal of RNA polymerase binds to FNR; When two binding sites are 6.5 bases apart, the C-terminus and N-terminus of RNA polymerase jointly bind to FNR. Based on this, we speculate that when the latter mechanism is combined, the energy reduction of the system is more significant, i.e. $\Delta e_ {FR}$ has a larger absolute value.
Based on this, we fixed other parameters in the model and adjust he value of $\Delta e_{FR}$. The value of this parameter in the original model is -8 ${k_b}T$ , and now observe the distribution of transcription rate and experimental data prediction when the energy term is taken as -6, -7, -9, -10, -11, -12 ${k_b}T$ units (Figure 9). We found that as the absolute binding energy between FNR and RNA polymerase increased, the overall transcription rate increased, but the targeting ability for the hypoxic and high lactate conditions corresponding to tumors $(lactate>10mM, oxygen<0.2)$decreased.WefoundthatastheabsolutebindingenergybetweenFNRandRNApolymeraseincreased,theoveralltranscriptionrateincreased,butthetargetingabilityforthehypoxicandhighlactateconditionscorrespondingtotumors$(lactate>10mM, oxygen<0.2)$ decreased. The reason for this phenomenon is that under aerobic conditions, although most DNA strands exist in the form of loops, when the absolute value of binding energy is high, DNA strands that do not exist in the form of loops are more in the form of FNR bound RNA polymerase, resulting in higher compositional expression of pPepT.
Based on this, we fixed other parameters in the model and adjust he value of $\Delta e_{FR}$. The value of this parameter in the original model is -8 ${k_b}T$ , and now observe the distribution of transcription rate and experimental data prediction when the energy term is taken as -6, -7, -9, -10, -11, -12 ${k_b}T$ units (Figure 9). We found that as the absolute binding energy between FNR and RNA polymerase increased, the overall transcription rate increased, but the targeting ability for the hypoxic and high lactate conditions corresponding to tumors (lactate>10mM, oxygen<0.2)decreased.WefoundthatastheabsolutebindingenergybetweenFNRandRNApolymeraseincreased,theoveralltranscriptionrateincreased,butthetargetingabilityforthehypoxicandhighlactateconditionscorrespondingtotumors(lactate>10mM, oxygen<0.2) decreased. The reason for this phenomenon is that under aerobic conditions, although most DNA strands exist in the form of loops, when the absolute value of binding energy is high, DNA strands that do not exist in the form of loops are more in the form of FNR bound RNA polymerase, resulting in higher compositional expression of pPepT.
