Pre-equilibrium properties of signaling dose-response curves allow discrimination between negative cooperativity and independent binding

ALEJANDRO COLMAN-LERNER; JUAN PABLO DI BELLA; FEDERICO SEVLEVER; ALEJANDRA C VENTURA

Buenos Aires

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

10 Sociedades Cientificas Argentinas

Previous works in cellular signaling propose to study pre-equilibrium properties in order to distinguish between negative cooperativity (NC) and independent binding (IB). We have already presented the existence of a mechanism known as Pre-Equilibrium Sensing and Signaling (PRESS), which allows cells to discriminate between signaling levels that saturate receptors in equilibrium.In this work, we combine analytical-computational studies of two toy models of a ligand-receptor binding with two binding sites, one model presenting NC and the other, IB. Using statistical analysis of the parameters space, we have discovered Hill coefficient pre-equilibrium general properties which allows to design new protocols of discrimination between NC and IB. We have tested the efficiency of these protocols for simulated data from both models and its dependency with noise from chemical reactions stochasticity.We found that pre-equilibrium Hill coefficient adds information and improves previous discrimination protocols.