Protein design

Protein design is the design of new protein molecules from scratch, or the deliberate design of a new molecule by making calculated variations on a known structure. The number of possible amino acid sequences is enormous, but only a subset of these sequences will fold reliably and quickly to a single native state. Protein design involves identifying such sequences, in particular those with a physiologically active native state. Protein design is a rational design technique used in protein engineering.
Protein design requires an understanding of the process by which proteins fold. In a sense it is the reverse of structure prediction: a tertiary structure is specified, and a primary sequence is identified which will fold to it.
Protein design is also referred to as inverse folding. From a physical point of view, the native state conformation of a protein is the free energy minimum for the protein chain, at least at biological temperatures (i.e. at temperatures between zero and a hundred degrees Celsius). Hence, designing a new protein involves the identification of the sequences which have the chosen structure as free energy minimum. This can be done by use of computer models, which, while simplifying the problem, are able to generate sequences to fold on the desired structure.
The design of minimalist computer models of proteins (lattice proteins), and the secondary structural modification of real proteins, began in the mid-1990s. The de novo design of real proteins became possible shortly afterwards, and the 21st century has seen the creation of small proteins with real biological function including catalysis and antiviral behaviour. There is great hope that the design of these and larger proteins will have application in medicine and bioengineering.