title: Predicting RNA pseudoknot folding thermodynamics.
abstract: Based on the experimentally determined atomic coordinates for RNA helices and the self-avoiding walks of the P (phosphate) and C4 (carbon) atoms in the diamond lattice for the polynucleotide loop conformations, we derive a set of conformational entropy parameters for RNA pseudoknots. Based on the entropy parameters, we develop a folding thermodynamics model that enables us to compute the sequence-specific RNA pseudoknot folding free energy landscape and thermodynamics. The model is validated through extensive experimental tests both for the native structures and for the folding thermodynamics. The model predicts strong sequence-dependent helix-loop competitions in the pseudoknot stability and the resultant conformational switches between different hairpin and pseudoknot structures. For instance, for the pseudoknot domain of human telomerase RNA, a native-like and a misfolded hairpin intermediates are found to coexist on the (equilibrium) folding pathways, and the interplay between the stabilities of these intermediates causes the conformational switch that may underlie a human telomerase disease.
authors.affiliation: Department of Physics, University of Missouri-Columbia Columbia, MO 65211, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Cao
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D019277:Entropy; D018965:Frameshifting, Ribosomal; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry; D019098:Telomerase / Q000737:chemistry; D016808:Tetrahymena thermophila / Q000201:enzymology; D013816:Thermodynamics; D014027:Tobacco Mosaic Virus / Q000235:genetics; D017806:Tymovirus / Q000235:genetics
chemical_list: D012367:RNA, Viral; C422952:telomerase RNA; D012313:RNA; D054303:HIV Reverse Transcriptase; D019098:Telomerase