A model of cooperativity based on restricted binding: kinetic and thermodynamic analysis

作者：Banerjee Kinshuk^*

来源：Journal of Mathematical Chemistry, 2014, 52(2): 741-753.

DOI：10.1007/s10910-013-0292-y

• Oligomeric protein
• Cooperativity
• Master equation
• Stochastic thermodynamics

Cooperative protein-ligand binding is an essential biochemical process. In this work, we introduce a model that can simulate the emergence of such phenomenon in the binding kinetics. It is based on the inability of the ligand molecules to fully utilize all the available binding sites due to some restriction, realized here in terms of a model parameter, called the restriction parameter. The theory is developed at the level of a single oligomeric protein molecule interacting with a ligand, maintained at a constant concentration, using a chemical master equation. The model provides stepwise binding constants related to the restriction parameter. The relative magnitudes of these constants, when compared to the Hill coefficients measuring cooperativity, give a physical insight in the development of the cooperative behavior and can also act as a reference frame. This can be useful for an alternative theoretical characterization of cooperativity in oligomeric proteins with large number of binding sites and arbitrary binding constants. We establish this point here by taking a tetrameric protein as a case study. A stochastic thermodynamic analysis is also performed, highlighting the energy-entropy contribution to the overall free energy change due to protein-ligand interaction for various cases of restricted binding.

• 出版日期2014-2