Discriminating between negative cooperativity and ligand binding to independent sites using pre-equilibrium properties of binding curves

摘要

Author summary When two successive events occur, it may make sense to know if they affect somehow each other, particularly if the properties of the second event are modified by the occurrence of the first one. Two scenarios lead to the same overall outcome: first, the two events are identical but they interfere with each other, and second, the two events are independent but non identical. The interference caused in the first scenario produces the same result as having a second event with different properties. Now, let's name these events as bindings, the interference as negative cooperativity, and the non-identical events as independent binding. In this work we focus on the dynamic process by which the two scenarios produce the same result. We selected a relevant but not characterized before property of the binding process, called its dynamic range, and found it behaves differently in these two scenarios and controlled by different parameters of interest. Based on this feature, we developed and algorithm to distinguish between negative cooperativity and independent binding based on the time evolution of the dynamic range. This tool allows to discover the microscopic model behind the data and may be useful in other similar problems in cell signaling.