Protein stability, aggregation, and crystallization are of fundamental scientific and technological importance. However, molecularly-detailed models that can account for both the proteins and the solvent are computationally prohibitive to study under relevant solution conditions. As a result, the relations between misfolding/aggregation events in solution and protein sequence (mutations), solvent conditions, solution composition, and the presence of interfaces are still poorly understood. Here, we introduce a strategy for investigating these phenomena through use of a new coarse-grained model that combines an analytical theory for heteropolymer collapse with a recently introduced model for solvation in aqeuous solution. This approach can qualitatively reproduce the basic effects of temperature, pressure, and sequence on protein stability. We have used the model to derive effective center-to-center interactions for native and denatured proteins. We are currently using these effective interactions as inputs to liquid-state theory and simulation to gain new insights into the global experimental behavior of protein solutions.