A Packing‐Density Metric for Exploring the Interior of Folded RNA Molecules

The intricate architectures of RNA molecules often contain expansive close-packed interfaces. The folding of the well-defined P4-P6 RNA domain was challenged by using a series of 2′-modified nucleotides with a narrow range of molecular volumes. The resulting folding interferences (see picture) reflect the spatial environment of the 2′-hydroxy groups and thereby define a packing-density metric.