Quantitative Categorization of Functional Dynamics of RNA Aptamers by Volume Change
Year: 2026
Type: article
Abstract: Nucleic acids act as functional materials by coupling the binding of small molecules with dynamic conformational changes. Although the characterization of the dynamics is informative for designing the aptamer and riboswitch, quantitative knowledge of the relationship between the function of nucleic acids and conformational dynamics has been limited. Analysis of the activity of a biomolecule as a function of pressure yields volumetric parameters, which provide information on conformational dynamics. Here, we investigated the binding of flavin mononucleotide (FMN) to the aptamer domain of the FMN riboswitch from Fusobacterium nucleatum under high pressure to quantitatively analyze the volume change (ΔV) during the complex formation. We show that the binding constant (Ka) at 25 °C between FMN and the FMN aptamer decreased with increasing pressure (1.21 × 106 M–1 at 0.1 MPa to 1.36 × 105 M–1 at 60 MPa). The ΔV of formation for the FMN/aptamer complex was 87.2 cm3 mol–1, which was much larger than the value for DNA duplex formation. Analyses of FMN aptamers with mutations in the stem regions showed that a high concentration of Mg2+ ions and poly(ethylene glycol), the latter as a crowding cosolute, decreased the ΔV drastically and synergistically. Our results demonstrate that both an excluded volume effect, occurring due to the exclusion of water during fluctuations of the aptamer before FMN binding, and dehydration upon FMN binding determine the function of the FMN riboswitch acting as a conformational selection model. Thus, analyses of volumetric parameters can be used to quantify the conformational dynamics of nucleic acids depending on their functions.
Source: ACS Measurement Science Au
Institution: Konan University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
Awards: G3129231701, G4972699534, G7327693839, Quantitative prediction of nucleic acid structures and functions affected by spaciotemporal environmental factors in cells, Pioneering next-generation statistical thermodynamics aimed at elucidating the functions of nucleic acid populations in the intracellular microenvironment, Elucidating the chemical basis of non-Watson-Crick base pairing that causes genomic variation
OpenAlex ID: W7171375536