G Protein-Coupled Receptor (GPCR) signaling is critical to a myriad of processes in the human body. Although the canonical signaling mechanism is well understood, there remain nuances to signaling that are poorly understood. In particular, signal modulation through the formation of both hetero- and homodimers has been identified as important for some receptors. However, the biological significance and the details of these interactions remain unclear and experimentally challenging to examine.  Here we present a computational approach that includes the contributions of multiple signaling species and downstream signaling via a coupled ordinary differential equation (ODE) system. With this model we can simulate the impact of key variables in the system (e.g. ligand affinities, receptor surface concentrations, or heterodimerization potential) and predict possible experimental outcomes, including downstream signaling, which may then be tested at the bench. These predictions will help inform a new generation of therapeutics that target signal modulation through dimerization, ultimately leading to better treatments and reduced side effects.

In silico analysis of GPCR dimerization and downstream signaling

245th National Meeting (2013)

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