A major challenge of computational protein design is the creation of novel proteins with arbitrarily chosen three-dimensional structures. Here, we used a general computional strategy that iterates between sequence design and structure prediction to design a 93-residue alpha/beta protein called Top7 with a novel sequence and topology. Top7 was found experimentally to be folded and extremely stable, and the x-ray crystal structure of Top7 is similar (root mean square deviation equals 1.2 angstroms) to the design model. The ability to design a new protein fold makes possible the exploration of the large regions of the protein universe not yet observed in nature. Superimposition of the Top7 computational model and x-ray structure shows the remarkable atomic-level accuracy of the design (1.2 angstrom RMSD). The backbones are respresented as ribbons (computational model : helices – dark blue, strands – red; x-ray structure : helices – light blue, strands – yellow), and selected amino-acid sidechains in the protein core are represented as sticks.