Dopamine binding to various dopamine receptors activates multiple intracellular signaling molecules, some of which interact with calcium activated signaling pathways. Many experiments measure agonist-stimulated elevations in signaling molecules using prolonged, diffuse application, whereas the response of neurons to transient and spatially localized stimuli is more important. Computational modeling is an approach for investigating the spatial extent, time course, and interaction of postsynaptic signaling molecules activated by dopamine and other transmembrane receptors. NeuroRD is a simulation algorithm which can simulate large numbers of pathways and molecules in multiple spines attached to a dendrite. We explain how to gather the information needed to develop computational models, to implement such models in NeuroRD, to perform simulations, and to analyze the simulated data from these models.