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- W2000644717 abstract "Naturally occurring chemoreceptors almost invariably employ structure-switching mechanisms, an observation that has inspired the use of biomolecular switches in a wide range of artificial technologies in the areas of diagnostics, imaging, and synthetic biology. In one mechanism for generating such behavior, clamp-based switching, binding occurs via the clamplike embrace of two recognition elements onto a single target molecule. In addition to coupling recognition with a large conformational change, this mechanism offers a second advantage: it improves both affinity and specificity simultaneously. To explore the physics of such switches we have dissected here the thermodynamics of a clamp-switch that recognizes a target DNA sequence through both Watson–Crick base pairing and triplex-forming Hoogsteen interactions. When compared to the equivalent linear DNA probe (which relies solely on Watson–Crick interactions), the extra Hoogsteen interactions in the DNA clamp-switch increase the probe’s affinity for its target by ∼0.29 ± 0.02 kcal/mol/base. The Hoogsteen interactions of the clamp-switch likewise provide an additional specificity check that increases the discrimination efficiency toward a single-base mismatch by 1.2 ± 0.2 kcal/mol. This, in turn, leads to a 10-fold improvement in the width of the “specificity window” of this probe relative to that of the equivalent linear probe. Given these attributes, clamp-switches should be of utility not only for sensing applications but also, in the specific field of DNA nanotechnology, for applications calling for a better control over the building of nanostructures and nanomachines." @default.
- W2000644717 created "2016-06-24" @default.
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- W2000644717 creator A5067240770 @default.
- W2000644717 date "2013-11-20" @default.
- W2000644717 modified "2023-10-03" @default.
- W2000644717 title "Thermodynamic Basis for Engineering High-Affinity, High-Specificity Binding-Induced DNA Clamp Nanoswitches" @default.
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- W2000644717 doi "https://doi.org/10.1021/nn404305e" @default.
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