General design principles for protein interaction specificity are challenging to extract. In DNA, specificity arises from a limited set of hydrogen-bonding interactions in the core of the double helix to design and build a wide range of shapes. In proteins, specificity arises largely from buried hydrophobic packing complemented by irregular peripheral polar interactions. Protein-based materials…

A central question in protein evolution is the extent to which naturally occurring proteins sample the space of folded structures accessible to the polypeptide chain. Repeat proteins composed of multiple tandem copies of a modular structure unit are widespread in nature and have critical roles in molecular recognition, signalling, and other essential biological processes. Naturally…

The prediction of the structures of proteins without detectable sequence similarity to any protein of known structure remains an outstanding scientific challenge. Here we report significant progress in this area. We first describe de novo blind structure predictions of unprecendented accuracy we made for two proteins in large families in the recent CASP11 blind test…