Ensemble Simulations: Folding, Unfolding and Misfolding of High-Efficiency Transfer-Messenger RNA Pseudoknot

The PK1 pseudoknot is a well-characterized super secondary structure from Aquifex aeolicus transfer-messenger RNA that participates in the ribosomal trans-translation rescue mechanism. Extensive all-atom molecular dynamics simulations were conducted across worldwide distributed computing network to study folding, unfolding, misfolding, and conformational plasticity of twenty-two nucleotide pseudoknot, yielding nearly 120 µs cumulative sampling time. Identification native non-native contacts throughout resulting data set was used as input for k-means clustering, which detected twenty-seven microstates sampled forty starting structures span spectrum between fold fully denatured state. Post-equilibration provide detailed depictions free energy landscape encompass native, unfolded, numerous intermediate misfolded states, well intricate folding mechanism motif. displays structural similarities class frameshifting pseudoknots suggests parallel trans-translational our previous potato leaf roll virus pseudoknot.