Publication

Abstract : In this work, we have introduced thermodynamic measure to characterize the nature of cooperativity in terms of the variation of standard free energy change with the fraction of ligand-bound sub-units of a protein in equilibrium, treating the protein-ligand attachment as a stochastic process. The fraction of ligandbound sub-units of cooperative ligand-binding processes are calculated by the formulation of stochastic master equation for both the KNF and MWC Allosteric cooperative model. The proposed criteria of this cooperative measurement is valid for all ligand concentrations unlike the traditional kinetic measurement of Hill coefficient at half-saturation point. A Kullback-Leibler distance is also introduced which indicates how much average standard free energy is involved if a non-cooperative system changes to a cooperative one, giving a quantitative synergistic measure of cooperativity as a function of ligand concentration which utilizes the full distribution function beyond the mean and variance. For the validation of our theory to provide a systematic approach to cooperativity, we have considered the experimental result of the cooperative binding of aspartate to the dimeric receptor of Salmonella typhimurium.