Receptor kinetics: Binding flux-based approaches offer complementary insight into how ligand binding evolves with
Georges Vauquelin1, Terry Kenakin2, Dominique Maes3
1Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium.
British Journal of Pharmacology
|July 31, 2026
Summary
Binding fluxes offer a dynamic perspective on ligand binding, complementing traditional rate constants. This approach provides deeper insights into binding mechanisms and predicts outcomes across various models.
Area of Science:
- Biophysics
- Biochemistry
- Pharmacology
Background:
- Traditional binding kinetics rely on rate constants.
- The concept of 'binding fluxes' offers a dynamic view of target/receptor state changes.
- Binding fluxes represent the rate of state transitions due to ligand binding or conformational shifts.
Purpose of the Study:
- To demonstrate the utility of binding fluxes in understanding ligand binding.
- To explore how binding fluxes provide additional insights beyond rate constants.
- To show the applicability of flux-based approaches to various ligand-binding models.
Main Methods:
- Simulated binding data using flux-based differential equations.
- Euler's method applied over small time intervals.
- Input parameters: ligand concentration(s) and rate constants.
Main Results:
- Binding fluxes offer more intuitive insights than complex algebraic expressions.
- Fluxes reveal transient binding overshoots and effects on ligand dissociation.
- Demonstrated the fundamental role of rate constants in all binding models.
Conclusions:
- Binding fluxes and rate constants are complementary for understanding binding processes.
- Flux-based approaches elucidate the 'how' and 'why' of binding evolution.
- Applicable to pre-equilibrium, equilibrium conditions, and all ligand-binding models.
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