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Dimerization of the receptor with the ligand binding to a monomer:
U_R2 model

In this model the receptor molecule dimerizes. Only the monomer is capable to appreciably bind the ligand. This mechanism is also relevant to cases of aggregation, where weak, fast-off dimerization promotes slow irreversible aggregation of the receptor.

Location

U_R2/

 

 

Contents

 

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Concentration dependence of R-R2 equilibrium

This is the simplest example. All species are in slow exchange, we will see three peaks. I set up simulation for the slow isomerization process with 3:1 ratio in favor of R* and nanomolar binding with very slow off-rate.

 

NOTE: ITC and smooth population curves will NOT work for changing concentration of the receptor!!!

 

Example_concentration_dependence/

Report: summary_report

slow dissociation

fast dissociation
Simulate setup_conc_dep U_R2_As_Bs_conc_dep Simulate setup_conc_dep U_R2_As_Bf_conc_dep

 

Conclusion

The model was reasonably reduced to the simple self-association model.

 

 

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U_R2 example 1: Slow dissociation, slow binding

Simulate setup U_R2_As_Bs

report: summary_report

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U_R2 example 2: Slow dissociation, fast binding

Simulate setup U_R2_Af_Bs

 

NOTE: This situation is VERY SIMILAR to behavior of U_R system. Use ITC profile to tell them apart.

 

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U_R2 example 3: Fast dissociation, fast binding

Simulate setup U_R2_Af_Bf

Note non-linearity of the FWHH curve shifted to 0.4 relatively to U_R model

The noted non-linearity makes the fit with the 2-site model fail miserably:

Such discrepancy between data and the fit is very remarkable, dissimilar to the U_R and, probably, to U_RL.

 

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U_R2 example 4: Fast dissociation, slow binding

Simulate setup U_R2_As_Bf

 

NOTE: This spectral appearance is VERY SIMILAR to U_RL model and U_R2L2

 

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Conclusions

  1. The model works.
  2. Fast dissociation/slow binding and slow diss/fast binding regimes have remarkable similarity to the U_R and U_RL models.
  3. It is clear that a concentration dependence of peak positions MUST be determined for any system before the line shape analysis is attemped.

 

 

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