PNAS: High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations

We report the de novo folding of three hyperstable RNA tetraloops
to 1–3 Å rmsd from their experimentally determined structures
using molecular dynamics simulations initialized in the
unfolded state. RNA tetraloops with loop sequences UUCG, GCAA,
or CUUG are hyperstable because of the formation of noncanonical
loop-stabilizing interactions, and they are all faithfully reproduced
to angstrom-level accuracy in replica exchange molecular
dynamics simulations, including explicit solvent and ion molecules.
This accuracy is accomplished using unique RNA parameters, in
which biases that favor rigid, highly stacked conformations are
corrected to accurately capture the inherent flexibility of ssRNA
loops, accurate base stacking energetics, and purine syn-anti interconversions…