title: Computational protein design with backbone plasticity.
abstract: The computational algorithms used in the design of artificial proteins have become increasingly sophisticated in recent years, producing a series of remarkable successes. The most dramatic of these is the de novo design of artificial enzymes. The majority of these designs have reused naturally occurring protein structures as 'scaffolds' onto which novel functionality can be grafted without having to redesign the backbone structure. The incorporation of backbone flexibility into protein design is a much more computationally challenging problem due to the greatly increased search space, but promises to remove the limitations of reusing natural protein scaffolds. In this review, we outline the principles of computational protein design methods and discuss recent efforts to consider backbone plasticity in the design process.
authors.affiliation: Centre for Synthetic Biology and Innovation, South Kensington Campus, London SW7 2AZ, U.K.|Section of Structural Biology, Department of Medicine, Imperial College London, London SW7 2AZ, U.K.
authors.forename: James T
authors.initials: JT
authors.lastname: MacDonald
authors.affiliation: Centre for Synthetic Biology and Innovation, South Kensington Campus, London SW7 2AZ, U.K.|Section of Structural Biology, Department of Medicine, Imperial College London, London SW7 2AZ, U.K.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Freemont
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D004798:Enzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D004798:Enzymes; D011506:Proteins
keywords: computational protein design; conformational sampling; flexible backbone design