title: Rational design of a structure-switching DNA aptamer for potassium ions.
abstract: 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.
authors.affiliation: Department of Chemistry, Penn State Altoona, Altoona, PA 16601, United States.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Catherine
authors.affiliation: Department of Chemistry, Penn State Altoona, Altoona, PA 16601, United States.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Shishido
authors.affiliation: Department of Chemistry and Biochemistry, Mercyhurst University, Erie, PA 16546, United States.
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Robbins-Welty
authors.affiliation: Department of Chemistry and Biochemistry, Mercyhurst University, Erie, PA 16546, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Diegelman-Parente
keywords: CD, circular dichroism; G-quartet; GQS, G-quartet sequence; Population-shift mechanism; Structure-switching aptamer; TBA, thrombin binding aptamer; Thrombin-binding aptamer; mFold