Guanidine-II aptamer conformations and ligand binding modes through the lens of molecular simulation

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Nucleic Acids Research. Oxford University Press. 2021, 49(14), pp. 7954-7965. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/gkab592
Zusammenfassung

Regulation of gene expression via riboswitches is a widespread mechanism in bacteria. Here, we investigate ligand binding of a member of the guanidine sensing riboswitch family, the guanidine-II riboswitch (Gd-II). It consists of two stem-loops forming a dimer upon ligand binding. Using extensive molecular dynamics simulations we have identified conformational states corresponding to ligand-bound and unbound states in a monomeric stem-loop of Gd-II and studied the selectivity of this binding. To characterize these states and ligand-dependent conformational changes we applied a combination of dimensionality reduction, clustering, and feature selection methods. In absence of a ligand, the shape of the binding pocket alternates between the conformation observed in presence of guanidinium and a collapsed conformation, which is associated with a deformation of the dimerization interface. Furthermore, the structural features responsible for the ability to discriminate against closely related analogs of guanidine are resolved. Based on these insights, we propose a mechanism that couples ligand binding to aptamer dimerization in the Gd-II system, demonstrating the value of computational methods in the field of nucleic acids research.

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ISO 690STEUER, Jakob, Oleksandra KUKHARENKO, Kai RIEDMILLER, Jörg S. HARTIG, Christine PETER, 2021. Guanidine-II aptamer conformations and ligand binding modes through the lens of molecular simulation. In: Nucleic Acids Research. Oxford University Press. 2021, 49(14), pp. 7954-7965. ISSN 0305-1048. eISSN 1362-4962. Available under: doi: 10.1093/nar/gkab592
BibTex
@article{Steuer2021-07-07Guani-54762,
  year={2021},
  doi={10.1093/nar/gkab592},
  title={Guanidine-II aptamer conformations and ligand binding modes through the lens of molecular simulation},
  number={14},
  volume={49},
  issn={0305-1048},
  journal={Nucleic Acids Research},
  pages={7954--7965},
  author={Steuer, Jakob and Kukharenko, Oleksandra and Riedmiller, Kai and Hartig, Jörg S. and Peter, Christine}
}
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