RNA is typically known for its participation in biology’s central dogma as an intermediate for protein production.  However, scientists demonstrated that 80% of the human genome is transcribed, yet only 2% is translated into protein.  Numerous non-translated sequences are conserved across mammals and distantly related eukaryotes, indicating that these structures have specific functions. It is thought these non-translated sequences regulate biological processes and/or diseases.  Understanding these RNAs will require efficient deciphering of their two- and three-dimensional structures, as well as understanding the relationship of structure to dynamics to function, a daunting task. Luckily, RNA tertiary structure is guided by motifs, conserved geometric structures of varying sequence that occur frequently in RNA, often with the same or related functions. Understanding the dynamics and stability of RNA motifs is pivotal to decoding the vast number of complex RNAs.<br/>We use adaptively biased molecular dynamics (ABMD) to study the sarcin/ricin domain (SRD), a common motif found from the ribosome to viroids. ABMD applies a bias that introduces a destabilizing force according to collective variables that ruptures the weakest part of the RNA first.  Our model allows comparison of the SRD with GC and AU regions of A-form RNA. <br/>Our model demonstrates that sufficient bias can disrupt each of the three regions of RNA. At a moderate bias potential all regions show distortions in pairing and stacking.  As the bias potential increases the AT region loses its pairing first, followed by the SRD and GC region. The spacers are the most resistant to disruption, especially the top one, reflecting the high stability of the upper block of the SRD.  As a control, a fully double stranded RNA with the same sequence as one of the strands was modeled.  Similar increased susceptibility of the AU region was seen.  We postulate that the SRD and GC regions are more tolerant of distortions in pairing and stacking than AU pairs. <br/>

Comparing the stability of the sarcin/ricin domain and A-form RNA using adaptively biased molecular dynamics

2019 Fall National Meeting

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