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Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.


Ribonucleic acid (RNA) molecules are known to undergo conformational changes in response to various environmental stimuli including temperature, pH, and ligands. In particular, viral RNA molecules are a key example of conformationally adapting molecules that have evolved to switch between many functional conformations. The transactivation response element (TAR) RNA from the type-1 human immunodeficiency virus (HIV-1) is a viral RNA molecule that is being increasingly explored as a potential therapeutic target due to its role in the viral replication process. In this work, we have studied the dynamics in TAR RNA in apo and liganded states by performing explicit-solvent molecular dynamics (MD) simulations initiated with 27 distinct structures. We determined that the TAR RNA structure is significantly stabilized on ligand binding with especially decreased fluctuations in its two helices. This rigidity is further coupled with the decreased flipping of bulge nucleotides, which were observed to flip more frequently in the absence of ligands. We found that initially-distinct structures of TAR RNA converged to similar conformations on removing ligands. We also report that conformational dynamics in unliganded TAR structures leads to the formation of binding pockets capable of accommodating ligands of various sizes.

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Physical Chemistry Chemical Physics


Royal Society of Chemistry

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This is an Open Access article published by Royal Society of Chemistry in Physical Chemistry Chemical Physics in 2021, available online: