Abstract
Aptamer selection can yield many oligonucleotides with different sequences and affinities for the target molecule. Here, we have combined computational and experimental approaches to understand if aptamers with different sequences but the same molecular target share structural and dynamical features. NEO1A, with a known NMR-solved structure, displays a flexible loop that interacts differently with individual aminoglycosides, its ligand affinities and specificities are responsive to ionic strength, and it possesses an adenosine in the loop that is critical for high-affinity ligand binding. NEO2A was obtained from the same selection and, although they are only 43% identical in overall sequence, NEO1A and NEO2A share similar loop sequences. Experimental analysis by 1D NMR and 2-aminopurine reporters combined with molecular dynamics modeling revealed similar structural and dynamical characteristics in both aptamers. These results are consistent with the hypothesis that the target ligand drives aptamer structure and also selects relevant dynamical characteristics for high-affinity aptamer-ligand interaction. Furthermore, they suggest that it might be possible to “migrate” structural and dynamical features between aptamer group members with different primary sequences but with the same target ligand.
Highlights
Aptamers are valuable as in vivo synthetic riboswitches and as in vitro sensors
With andriboswitches riboswitchesand andin inview viewof ofthe thelimited limitednumber numberof ofavailable availablesolved solvedaptamer aptamerstructures, structures,ititseems seems and highly unlikely that the structures of most aptamers will ever be solved to the atomic level by current highly unlikely that the structures of most aptamers will ever be solved to the atomic level by current biophysical approaches
Understanding understandinghow hownucleic nucleicacid acid aptamers interact with their ligands otherother molecules in their is essential for developing effective effective sensors, targeting and molecules in environment their environment is essential for developing sensors, molecules targeting
Summary
Aptamers are valuable as in vivo synthetic riboswitches and as in vitro sensors. They are useful subjects for studies of small molecule interactions with RNAs, especially when physical structural information (such as NMR or X-ray crystallographic data) is available. There are few solved structures of aptamer–small ligand complexes and even fewer of unoccupied aptamers. Knowledge of the dynamical aspects of aptamer–small molecule ligand interactions is largely absent. To fill these gaps, computational renderings of the dynamics of molecular interactions are being increasingly adopted as a means of expanding our understanding of RNA-small molecule functional complexity and dynamics [1,2,3,4]. A single SELEX (Systematic Evolution of Ligands by EXponential Enrichment) experiment
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