page_title: Protein design
section_title: Target structure
hierarchical_section_title: Protein design / Underlying models of protein structure and function / Target structure
caption_attribution_description: English: Ribbon diagram of the Top 7, computationally designed protein, based on the structure PDB id: 1QYS. The fold corresponds to one not seen previously on nature. For more information see: Kuhlman, Brian, et al. "Design of a novel globular protein fold with atomic-level accuracy." Science 302.5649 (2003): 1364-1368.
context_page_description: Protein design is the rational design of new protein molecules to design novel activity, behavior, or purpose, and to advance basic understanding of protein function. Proteins can be designed from scratch or by making calculated variants of a known protein structure and its sequence. Rational protein design approaches make protein-sequence predictions that will fold to specific structures. These predicted sequences can then be validated experimentally through methods such as peptide synthesis, site-directed mutagenesis, or artificial gene synthesis.
  Rational protein design dates back to the mid-1970s. Recently, however, there were numerous examples of successful rational design of water-soluble and even transmembrane peptides and proteins, in part due to a better understanding of different factors contributing to protein structure stability and development of better computational methods.
context_section_description: 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. The protein Top7, developed in David Baker's lab, was designed completely using protein design algorithms, to a completely novel fold. More recently, Baker and coworkers developed a series of principles to design ideal globular-protein structures based on 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.
caption: The Top7 protein was one of the first proteins designed for a fold that had never been seen before in nature[6]
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