title: Combining Design and Selection to Create Novel Protein-Peptide Interactions.
abstract: The ability to design new protein-protein interactions (PPIs) has many applications in biotechnology and medicine. The goal of designed PPIs is to achieve both high affinity and specificity for the target protein. A great challenge in protein design is to identify such proteins from an enormous number of potential sequences. Many computational and experimental methods have been developed to contend with this challenge. Here we describe one particularly powerful approach-semirational design-that combines design and selection. This approach has been applied to generate new PPIs for many applications, including novel affinity reagents for protein detection/purification and bioorthogonal modules for synthetic biology (Jackrel, Valverde, & Regan, 2009; Sawyer et al., 2014; Speltz, Brown, Hajare, Schlieker, & Regan, 2015; Speltz, Nathan, & Regan, 2015).
authors: Department of Chemistry, Yale University, New Haven, CT, United States.
authors: E B
authors: EB
authors: Speltz
authors: Department of Chemistry, Yale University, New Haven, CT, United States.
authors: N
authors: N
authors: Sawyer
authors: Department of Chemistry, Yale University, New Haven, CT, United States. Electronic address: lynne.regan@yale.edu.
authors: L
authors: L
authors: Regan
mesh_terms: D002846:Chromatography, Affinity; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods*; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010455:Peptides; D011506:Proteins
keywords: Bimolecular fluorescence complementation assay; Protein complementation assay; Protein design; Protein–protein interactions; Rational protein design; Split GFP; Split mCherry; Structure-guided design