Some mutations were like a tax rebate and raised the propensity of TAR to adopt its biologically active structures, while other modifications raised the tax and decreased the odds that TAR would adopt a biologically active structure.

Hidden mechanism may lead to new drugs

“What we found was a hidden mechanism for controlling the activity of a molecule in a cell,” says Al-Hashimi. By altering the propensity of TAR to form biologically active states—by changing the tax rate—the researchers could fine-tune the molecule’s activity in cells.

Just as space holds infinite mysteries, when we zoom in at the level of biomolecules (one trillion times smaller than a meter), there is still so much to learn.

Rensselaer Polytechnic Institute’s Catherine Royer is dedicated to understanding the conformational landscapes of biomolecules and how they modulate cell function. When biomolecules receive certain inputs, it can cause the atoms to rearrange and the biomolecule to change shape. This change in shape affects their function in cells, so understanding conformational dynamics is critical for drug development.

In research recently published in the Proceedings of the National Academy of Sciences, Royer and her team examined the conformational dynamics of a human transfer ribonucleic acid (tRNA) under high hydrostatic pressure. The high pressure led to an increased population of the tRNA-excited states that normally exist at very low levels, allowing new insights into tRNA function.