Background: Aptamers are RNA/DNA biomolecules representing an emerging class of protein interactors and regulators. Despite the growing interest in these molecules, current understanding of chemical-physical basis of their target recognition is limited. Recently, the characterization of the aptamer targeting the protein-S8 has suggested that flexibility plays important functional roles. We investigated the structural versatility of the S8-aptamer by molecular dynamics simulations.
Methods: Five different simulations have been conducted by varying starting structures and temperatures.
Results: The simulation of S8-aptamer complex provides a dynamic view of the contacts occurring at the complex interface. The simulation of the aptamer in ligand-free state indicates that its central region is intrinsically endowed with a remarkable flexibility. Nevertheless, none of the trajectory structures adopts the structure observed in the S8-aptamer complex. The aptamer ligand-bound is very rigid in the simulation carried out at 300 K. A structural transition of this state, providing insights into the aptamer-protein recognition process, is observed in a simulation carried out at 400 K. These data indicate that a key event in the binding is linked to the widening of the central region of the aptamer. Particularly relevant is switch of the A26 base from its ligand-free state to a location that allows the G13-C28 base-pairing.
Conclusions: Intrinsic flexibility of the aptamer is essential for partner recognition. Present data indicate that S8 recognizes the aptamer through an induced-fit rather than a population-shift mechanism.
General significance: The present study provides deeper understanding of the structural basis of the structural versatility of aptamers.
Keywords: Aptamer conformational flexibility; Molecular dynamics; Population shift mechanism; Protein-nucleic acid recognition; Ribosomal proteins.
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