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Using the Population‐Shift Mechanism to Rationally Introduce “Hill‐type” Cooperativity into a Normally Non‐Cooperative Receptor
Author(s) -
Simon Anna J.,
ValléeBélisle Alexis,
Ricci Francesco,
Watkins Herschel M.,
Plaxco Kevin W.
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201403777
Subject(s) - cooperativity , allosteric regulation , cooperative binding , biophysics , population , chemistry , receptor , nanotechnology , combinatorial chemistry , computational biology , binding site , materials science , biology , biochemistry , demography , sociology
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.