Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 541661
Title Probing ATP/ATP-Aptamer or ATP-Aptamer Mutant Complexes by Microscale Thermophoresis and Molecular Dynamics Simulations : Discovery of an ATP-Aptamer Sequence of Superior Binding Properties
Author(s) Biniuri, Yonatan; Albada, Bauke; Willner, Itamar
Source The Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical (2018). - ISSN 1520-6106 - 8 p.
DOI https://doi.org/10.1021/acs.jpcb.8b06802
Department(s) Laboratory for Organic Chemistry
Publication type Refereed Article in a scientific journal
Publication year 2018
Abstract

Microscale thermophoresis (MST) is used to follow the dissociation constants corresponding to ATTO 488-labeled adenosine triphosphate (ATP) and the ATP-aptamer or ATP-aptamer mutants that include two binding sites for the ATP ligand. A set of eight ATP-aptamer mutants, where the thymidine bases, within the reported ATP binding aptamer sites, are substituted with cytosine bases, are examined. The MST-derived dissociation constant of ATP to the reported aptamer is Kd = 31 ± 3 μM, whereas most of the aptamer mutants show lower affinity (higher Kd values) toward the ATP ligand. One aptamer mutant reveals, however, a higher affinity toward the ATP ligand, as compared to the reported ATP-aptamer. Molecular dynamics and docking simulations identify the structural features that control the affinities of binding of the ATP ligand to the two binding sites associated with the ATP-aptamer or the ATP-aptamer mutants. The simulated structures suggest that H-bonds between the ATP ligand and G9 and G11 bases, within one binding domain, and the π- π interactions between G6 and the ATP purine moiety and the pyrimidine ring, in the second binding domain, control the affinity of binding interactions between the ATP ligand and the ATP-aptamer or ATP-aptamer mutant. Very good correlation between the computed Kd values and the MST-derived Kd values is found. The ATP-aptamer mutant (consisting of A1→ G, T4 → C, T12 → C, A24 → G, and T27 → C mutations) reveals superior binding affinities toward the ATP ligands (Kd = 15 ± 1 μM) as compared to the binding affinity of ATP to the reported aptamer. These features of the mutant are supported by molecular dynamics simulations.

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