A 'protein design cycle', involving cycling between theory and experiment, has led to recent advances in rational protein design. A reductionist approach, in which protein positions are classified by their local environments, has aided development of an appropriate energy expression. The computational principles and practicalities of the protein design cycle are discussed.

Protein engineering is at an exciting stage because designed protein-protein interactions are being used in many applications. For instance, three designed proteins are now in clinical trials. Although there have been many successes over the last decade, protein engineering still faces numerous challenges. Often, designs do not work as anticipated and they still require substantial redesign. Th...

Combinatorial protein libraries permit the examination of a wide range of sequences. Such methods are being used for denovo design and to investigate the determinants of protein folding. The exponentially large number of possible sequences, however, necessitates restrictions on the diversity of sequences in a combinatorial library. Recently, progress has been made in developing theoretical tool...