Editing Protein design (section)

===Sequence space===
[[File:1FSVblue-1ZAAred.png|thumb|FSD-1 (shown in blue, PDB id: 1FSV) was the first ''de novo'' computational design of a full protein.<ref name="dahiyat1997">{{cite journal|last=Dahiyat|first=BI|author2=Mayo, SL |title=De novo protein design: fully automated sequence selection.|journal=Science|date=October 3, 1997|volume=278|issue=5335|pages=82–7|pmid=9311930|doi=10.1126/science.278.5335.82|citeseerx=10.1.1.72.7304}}</ref> The target fold was that of the zinc finger in residues 33–60 of the structure of protein Zif268 (shown in red, PDB id: 1ZAA). The designed sequence had very little sequence identity with any known protein sequence.]]

In rational protein design, proteins can be redesigned from the sequence and structure of a known protein, or completely from scratch in ''de novo'' protein design. In protein redesign, most of the residues in the sequence are maintained as their wild-type amino-acid while a few are allowed to mutate. In ''de novo'' design, the entire sequence is designed anew, based on no prior sequence.

Both ''de novo'' designs and protein redesigns can establish rules on the [[Sequence space (evolution)|sequence space]]: the specific amino acids that are allowed at each mutable residue position. For example, the composition of the surface of the [[#Protein resurfacing|RSC3 probe]] to select HIV-broadly neutralizing antibodies was restricted based on evolutionary data and charge balancing.  Many of the earliest attempts on protein design were heavily based on empiric ''rules'' on the sequence space.<ref name="richardson1989" /> Moreover, the [[#Design of fibrous proteins|design of fibrous proteins]] usually follows strict rules on the sequence space. [[Collagen]]-based designed proteins, for example, are often composed of Gly-Pro-X repeating patterns.<ref name="richardson1989" /> The advent of computational techniques allows designing proteins with no human intervention in sequence selection.<ref name="dahiyat1997" />