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

Abstract

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 a worldwide distributed computing network to study the folding, unfolding, misfolding, and conformational plasticity of the twenty-two nucleotide PK1 pseudoknot, yielding nearly 120 µs of cumulative sampling time. Identification of native and non-native contacts throughout the resulting data set was used as input for k-means clustering, which detected twenty-seven conformational microstates sampled from forty starting structures that span the spectrum between the native fold and the fully denatured state.