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Investigations of the Folding Dynamics of the RNA Pseudoknot Structural Motif via Massively Parallel Molecular Dynamics
Author(s) -
Pham Benjamin D.,
Kusaba Carolyn C.,
Bakhom Mona,
Wang Richard,
Sorin Eric J.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb100
Subject(s) - pseudoknot , rna , hairpin ribozyme , computational biology , ribozyme , molecular dynamics , aquifex aeolicus , topology (electrical circuits) , computer science , physics , biology , chemistry , mathematics , genetics , gene , computational chemistry , combinatorics , escherichia coli
RNA pseudoknots compose a three‐dimensional structural motif that is present in the catalytic cores of some ribozymes, and are also capable of stimulating ribosomal frameshifts. Furthermore, their complex topology and non‐canonical hairpin‐loop composition make pseudoknots an essential structural motif with which to study the RNA folding process. Here we report our analysis of nearly 20,000 independent all‐atom molecular dynamics simulations of the ribosomal frame‐shifting pseudoknot of Luteovirus and the tmRNA pseudoknot from Aquifex aeolicus , which share global topology but have only ~50% sequence similarity. Using the Folding@Home distributed computing network and our new Pathway Enumeration sampling method, a cumulative sampling time of over 100 μs was achieved for each of these pseudoknots. K‐means clustering was used to identify 27 conformational microstates for each pseudoknot and similar folding pathways were identified for these two sequences. In agreement with our earlier work, this study suggests that native state topology is a predominate factor in the RNA folding mechanism. This work was made possible by the worldwide Folding@Home volunteers who contributed invaluable processor time, Women & Philanthropy, and a Research Corporation Cottrell College Science Award.