Despite the remarkable success of combination antiretroviral therapy, HIV-1 remains among the major causes of human suffering and loss of life in poor and developing nations. To prevail in this drawn-out battle with the pandemic, it is essential to continue developing advanced antiviral agents to fight drug resistant HIV-1 variants.
Ribonucleic acids (RNAs) are conformationally flexible molecules that fold into three-dimensional structures and play an important role in different cellular processes as well as in the development of many diseases. RNA has therefore become an important target for developing novel therapeutic approaches. The biophysical processes underlying RNA function are often associated with rare structural transitions that play a key role in ligand recognition. In this work, we probe these rarely occurring transitions using nonequilibrium simulations by characterizing the dissociation of a ligand molecule from an HIV-1 viral RNA element. Specifically, we observed base-flipping rare events that are coupled with ligand binding/unbinding and also provided mechanistic details underlying these transitions.
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...
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