Editing Protein design (section)

===Target structure===
[[File:Top7.png|thumb|left|The [[Top7]] protein was one of the first proteins designed for a fold that had never been seen before in nature<ref name="kuhlman03">{{cite journal|last=Kuhlman|first=B|author2=Dantas, G |author3=Ireton, GC |author4=Varani, G |author5=Stoddard, BL |author6= Baker, D |title=Design of a novel globular protein fold with atomic-level accuracy.|journal=Science|date=November 21, 2003|volume=302|issue=5649|pages=1364–8|pmid=14631033|bibcode= 2003Sci...302.1364K |doi= 10.1126/science.1089427|s2cid=1939390}}</ref>]]

Protein function is heavily dependent on protein structure, and rational protein design uses this relationship to design function by designing proteins that have a target structure or fold. Thus, by definition, in rational protein design the target structure or ensemble of structures must be known beforehand. This contrasts with other forms of protein engineering, such as [[directed evolution]], where a variety of methods are used to find proteins that achieve a specific function, and with [[protein structure prediction]] where the sequence is known, but the structure is unknown.

Most often, the target structure is based on a known structure of another protein. However, novel folds not seen in nature have been made increasingly possible. Peter S. Kim and coworkers designed trimers and tetramers of unnatural coiled coils, which had not been seen before in nature.<ref name="gordon99review" /><ref name="harbury99" /> The protein Top7, developed in [[David Baker (biochemist)|David Baker]]'s lab, was designed completely using protein design algorithms, to a completely novel fold.<ref name="kuhlman03" /> More recently, Baker and coworkers developed a series of principles to design ideal [[globular protein|globular-protein]] structures based on [[folding funnel|protein folding funnels]] that bridge between secondary structure prediction and tertiary structures. These principles, which build on both protein structure prediction and protein design, were used to design five different novel protein topologies.<ref>{{cite journal|last=Höcker|first=B|title=Structural biology: A toolbox for protein design.|journal=Nature|date=November 8, 2012|volume=491|issue=7423|pages=204–5|pmid=23135466|bibcode= 2012Natur.491..204H |doi= 10.1038/491204a|s2cid=4426247|doi-access=free}}</ref>