ArticleProceedings of the National Academy of Sciences of the United States of America2009
Thermodynamic basis for the optimization of binding-induced biomolecular switches and structure-switching biosensors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed.
- Entropy-Driven Physical Amplification in Multivalent Biosensing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecular engineering of CRISPR/Cas12a: from activity enhancement to exponential signal amplification.Chemical science · 2026Review
- A biochemical sensor with continuous extended stability in vivo.Nature biomedical engineering · 2025Article
- Synthetic CRISPR Networks Driven by Transcription Factors via Structure-Switching DNA Translators.Journal of the American Chemical Society · 2025Article
- Simultaneous, Seconds-Resolved Doxorubicin Measurements in the Blood and Subcutaneous Interstitial Fluid Identify Quantitative Pharmacokinetic Relationships between the Two.ACS pharmacology & translational science · 2025Article
- Generalizable Molecular Switch Designs forAccounts of chemical research · 2025Article
- Rationally Designed DNA-Based Scaffolds and Switching Probes for Protein Sensing.Advances in biochemical engineering/biotechnology · 2024Review
- Enthalpy and entropy synergistic regulation-based programmable DNA motifs for biosensing and information encryption.Science advances · 2023Article
- Functional advantages of building nanosystems using multiple molecular components.Nature chemistry · 2023Article
- Using Spectroscopy to Guide the Adaptation of Aptamers into Electrochemical Aptamer-Based Sensors.Bioconjugate chemistry · 2023Article
- DNA mechanical flexibility controls DNA potential to activate cGAS-mediated immune surveillance.Nature communications · 2022Article
- Programmable self-regulated molecular buffers for precise sustained drug delivery.Nature communications · 2022Article
- Critical Design Factors for Electrochemical Aptasensors Based on Target-Induced Conformational Changes: The Case of Small-Molecule Targets.Biosensors · 2022Review
- Enhancement of CRISPR/Cas12a trans-cleavage activity using hairpin DNA reporters.Nucleic acids research · 2022Article
- Dissipative DNA nanotechnology.Nature chemistry · 2022Review
- DNA-Based Nanoswitches: Insights into Electrochemiluminescence Signal Enhancement.Analytical chemistry · 2021Article
- Folding-upon-Repair DNA Nanoswitches for Monitoring the Activity of DNA Repair Enzymes.Angewandte Chemie (International ed. in English) · 2021Article
- Thermodynamic analysis of cooperative ligand binding by the ATP-binding DNA aptamer indicates a population-shift binding mechanism.Scientific reports · 2020Article
- Expanding detection windows for discriminating single nucleotide variants using rationally designed DNA equalizer probes.Nature communications · 2020Article
- Re-Evaluating the Conventional Wisdom about Binding Assays.Trends in biochemical sciences · 2020Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Binding-induced biomolecular switches are used throughout nature and, increasingly, throughout biotechnology for the detection of chemical moieties and the subsequent transduction of this detection into useful outputs. Here we show that the thermodynamics of these switches are quantitatively described by a simple 3-state population-shift model, in which the equilibrium between a nonbinding, nonsignaling state and the binding-competent, signaling state is shifted toward the latter upon target binding. Because of this, their performance is determined by the tradeoff inherent to their switching thermodynamics; while a switching equilibrium constant favoring the nonbinding, nonsignaling, conformation ensures a larger signal change (more molecules are poised to respond), it also reduces affinity (binding must overcome a more unfavorable conformational free energy). We then derive and employ the relationship between switching thermodynamics and switch signaling to rationally tune the dynamic range and detection limit of a representative structure-switching biosensor, a molecular beacon, over 4 orders of magnitude. These findings demonstrate that the performance of biomolecular switches can be rationally tuned via mutations that alter their switching thermodynamics and suggest a mechanism by which the performance of naturally occurring switches may have evolved.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.