Cooperativity concepts in protein binding models--problems of cooperativity definition, detection, identification and measuring

Cooperativity in protein-ligand binding cannot yet be treated as a urinary phenomenon (neither in investigating nor in modelling), although imaginable to rest upon some few general principles only. Knowledge of atomic details of protein-ligand interactions is still limited. Instead of a physico-chemical explanation and definition of cooperativity, a series of schematic concept has been established throughout the literature. Some dominating or merely observable features are isolated and intermixed with plausibly invented mechanistic details. These cooperativity concepts are put together and partly generalized here. From comparing these concepts with the state of binding theory on the one hand and with the nature of measured binding data on the other, some problems of understanding cooperative effects and of detecting, measuring and identifying them are pointed out. For special cases, suitable criteria and measures are recommended and graphic and mathematical techniques discussed. The limited significance and generality of current cooperativity terms is emphasized. Some different levels of understanding have to be distinguished.