Explore the contents of this article with a free Wolfram SystemModeler trial. Yesterday, the Nobel Prize in Chemistry was awarded to Robert J. Lefkowitz and Brian K. Kobilka for having mapped how a family of cellular receptors called G-protein-coupled receptors (GPCRs) work. The Nobel Prize winners' research has proven to be very important in the development of novel therapeutic drugs—about 40–50% of all therapeutic drugs in use today are centered on GPCRs. The real beauty of GPCR-based response systems is that they include components that are used over and over again for the response to external signals in many kinds of cellular functions throughout our bodies. Sight, smell, and the adrenaline response are examples of these GPCR-mediated responses with physiologically important functions. Identifying new targets for therapeutic drug intervention includes analysis of the complex webs of signaling pathways and feedback systems in our cells, extending beyond the first event of a signal connecting with the GPCR on the cell surface, which is non-trivial. Lately the cost-effective practice of using mathematical models as an initial step for finding those elusive new targets, and also as a tool for understanding how other reactions of a cell might be affected by a new drug, has been growing. In this blog post we are going to use modeling and simulation in order to illustrate how the GPCR-based cellular response to an external signal can be modified. And by performing this analysis, I thought we should also see how we can find promising targets for therapeutic drug design, which are then aimed at either increasing or decreasing the response. Since the first two steps in the pathways are identical in most of the GPCR-based signal responses in a cell, we can freely choose a representative model. One such well understood signal response pathway that uses GPCR is the mating pheromone response in yeast, which we are here going to explore using Mathematica and Wolfram SystemModeler.