Allosteric conformational ensembles have unlimited capacity for integrating information

Integration of binding information by macromolecular entities is fundamental to cellular functionality. Recent work has shown that such integration cannot be explained pairwise cooperativities, in which modulated at another site. Higher-order cooperativities (HOCs), collectively multiple other events, appear necessary but an appropriate mechanism been lacking. We show here HOCs arise through allostery, effective cooperativity emerges indirectly from ensemble dynamically interchanging conformations. Conformational ensembles play important roles many processes their integrative capabilities remain poorly understood. sufficiently complex can implement any form achievable without energy expenditure, including all patterns HOCs. Our results provide a rigorous biophysical foundation for analysing the allostery. discuss implications eukaryotic gene regulation, where conformational dynamics accompanies widespread integration.