We model all different aspects of μ-opioid receptor activation. This starts with the binding of an opioid to the receptor, followed by conformnational changes, spatio-temporal resolved signaling processes in the cell, the signaling effects, and the internalization and recovering of the μ-opioid receptor via the arrestin route. For this goal we need to model non-reversible molecular and signaling processes. The scientific goal is to estimate missing parameters, characteristic time-scales of the elementary steps, and coherent structures of non-reversible processes from (also experimental) data.
Figure 1: Reaction network for the signaling pathway. The receptor cycle is connected to the G-protein cycle and further to the signal cycle of membrane calcium channel modulation. We analyze the effect of NFEPP in comparison to fentanyl at different pH-levels and oxygen radical levels. The dynamics are studied using deterministic models in form of reaction rate equations and by stochastic models in form of Markov jump processes.
Figure 2: Experimental in vitro data and optimally fitted ODE model. Dots represent the time course of ligand-induced G-protein subunit dissociation measured by FRET in HEK293 cells. FRET values were transformed into concentration of undissociated G-proteins by a scaling factor. Lines indicate the best-fit of the ODE model to the data.
