title: Using the population-shift mechanism to rationally introduce "Hill-type" cooperativity into a normally non-cooperative receptor.
abstract: Allosteric cooperativity, which nature uses to improve the sensitivity with which biomolecular receptors respond to small changes in ligand concentration, could likewise be of use in improving the responsiveness of artificial biosystems. Thus motivated, we demonstrate here the rational design of cooperative molecular beacons, a widely employed DNA sensor, using a generalizable population-shift approach in which we engineer receptors that equilibrate between a low-affinity state and a high-affinity state exposing two binding sites. Doing so we achieve cooperativity within error of ideal behavior, greatly steepening the beacon's binding curve relative to that of the parent receptor. The ability to rationally engineer cooperativity should prove useful in applications such as biosensors, synthetic biology and "smart" biomaterials, in which improved responsiveness is of value.
authors.affiliation: Biomolecular Science and Engineering Program, UC Santa Barbara, Santa Barbara, CA 93106 (USA).
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Simon
authors.forename: Alexis
authors.initials: A
authors.lastname: Vallée-Bélisle
authors.forename: Francesco
authors.initials: F
authors.lastname: Ricci
authors.forename: Herschel M
authors.initials: HM
authors.lastname: Watkins
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Plaxco
mesh_terms: D001665:Binding Sites; D001672:Biocompatible Materials; D015374:Biosensing Techniques; D004247:DNA / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015202:Protein Engineering; D011955:Receptors, Drug / Q000737:chemistry* / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D008024:Ligands; D011955:Receptors, Drug; D004247:DNA
keywords: DNA; allosterism; cooperative effects; sensors; synthetic biology