Rational design of a structure-switching DNA aptamer for potassium ions.
Rational design of a structure-switching DNA aptamer for potassium ions.
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DOI：
10.1016/j.fob.2014.08.008
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发表时间：
2014
期刊：
影响因子：
2.6
通讯作者：
Diegelman-Parente, Amy
中科院分区：
文献类型：
--
作者：
Catherine, Andrew T.;Shishido, Stephanie N.;Robbins-Welty, Gregg A.;Diegelman-Parente, Amy
We report the rational design of structure-switching DNA aptamers for potassium. The shift between non-binding and binding-competent states was determined experimentally. The stability of the non-binding state was estimated computationally. A linear free energy relationship between these values was established. Structure-switching molecules provide a unique means for analyte detection, generating a response to analyte concentration through a binding-specific conformational change between non-binding and binding-competent states. While most ligand-binding molecules are not structure switching by default, many can be engineered to be so through the introduction of an alternative non-binding (and thus non-signalling) conformation. This population-shift mechanism is particularly effective with oligonucleotides and has led to the creation of structure-switching aptamers for many target ligands. Here, we report the rational design of structure-switching DNA aptamers, based on the thrombin binding aptamer (TBA), that bind potassium with affinities that bridge the gap between previously reported weak-binding and strong-binding aptamers. We also demonstrate a correlation between the free energy of the experimentally determined binding affinity for potassium and the computationally estimated free energy of the alternative (non-binding) structure.
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