The regulation of many cellular functions involves receptor-mediated transmission of chemical or physical information across the extracellular membrane. These processes entail cooperative interactions and structural changes within and between multiple macromolecular entities that can range in size from a few hundred to several thousand amino acids. The size of these macromolecular systems as well as the complexity of the environment in which they evolve present formidable challenges for computational simulation approaches aimed at determining the molecular bases of the interactions and structural changes that underlie the transmission of the information across the membrane. Elucidating these mechanisms is key to understanding the normal function of transmembrane receptors but is also key to developing therapeutic strategies that can target effectively the dysfunctional and disease-related states of these receptors. To address these challenges we have undertaken a systematic approach for the development of coarse-grained representations of macromolecular entities. This approach keeps a residue-level description of macromolecules in order to maintain a direct link with experimental approaches that can probe the effects of single residue substitutions. Similarly, in order to maintain simulation conditions that describe as realistically as possible the environments in which these entities evolve, we keep explicit representations of aqueous and lipid molecules. Here, I present results which show that our approach can reliably reproduce the conformational dynamics and known structural transitions for a number of macromolecular systems, rivaling in accuracy all-atom computational approaches such as normal modes analysis and molecular dynamics simulations, but at less than 1/10th of the computational cost.