All cellular functions are governed by a complex network of signaling pathways involving interactions between hundreds of proteins. When these networks are perturbed by mutations or environmental disturbances, diseases, such as cancer, can result. For each of these proteins to function properly, their interactions with other proteins must be precisely regulated in a manner that is responsive to the environment both inside and outside the cell. Therefore a detailed knowledge of how proteins recognize and bind to the correct protein targets is required to elucidate the processes that go awry in disease states. In this proposal, we study a particularly common protein-protein interaction domain, called the SH3 domain, and use yeast as a model system to study the function of these domains. Our work utilizes an innovative combination of in vitro characterization of mutant proteins, computational studies, and biological assays in yeast. The goals of this work are to understand how proteins specifically recognize other proteins and how this recognition impacts the functioning of the cell.