title: Evaluating and learning from RNA pseudotorsional space: quantitative validation of a reduced representation for RNA structure.
abstract: Quantitatively describing RNA structure and conformational elements remains a formidable problem. Seven standard torsion angles and the sugar pucker are necessary to characterize the conformation of an RNA nucleotide completely. Progress has been made toward understanding the discrete nature of RNA structure, but classifying simple and ubiquitous structural elements such as helices and motifs remains a difficult task. One approach for describing RNA structure in a simple, mathematically consistent, and computationally accessible manner involves the invocation of two pseudotorsions, eta (C4'(n-1), P(n), C4'(n), P(n+1)) and theta (P(n), C4'(n), P(n+1), C4'(n+1)), which can be used to describe RNA conformation in much the same way that varphi and psi are used to describe backbone configuration of proteins. Here, we conduct an exploration and statistical evaluation of pseudotorsional space and of the Ramachandran-like eta-theta plot. We show that, through the rigorous quantitative analysis of the eta-theta plot, the pseudotorsional descriptors eta and theta, together with sugar pucker, are sufficient to describe RNA backbone conformation fully in most cases. These descriptors are also shown to contain considerable information about nucleotide base conformation, revealing a previously uncharacterized interplay between backbone and base orientation. A window function analysis is used to discern statistically relevant regions of density in the eta-theta scatter plot and then nucleotides in colocalized clusters in the eta-theta plane are shown to have similar 3-D structures through RMSD analysis of the RNA structural constituents. We find that major clusters in the eta-theta plot are few, underscoring the discrete nature of RNA backbone conformation. Like the Ramachandran plot, the eta-theta plot is a valuable system for conceptualizing biomolecular conformation, it is a useful tool for analyzing RNA tertiary structures, and it is a vital component of new approaches for solving the 3-D structures of large RNA molecules and RNA assemblies.
authors: Department of Physics, Columbia University, New York, NY 10027, USA.
authors: Leven M
authors: LM
authors: Wadley
authors: Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
authors: Kevin S
authors: KS
authors: Keating
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
authors: Carlos M
authors: CM
authors: Duarte
authors: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA. Electronic address: anna.pyle@yale.edu.
authors: Anna Marie
authors: AM
authors: Pyle
mesh_terms: D016000:Cluster Analysis; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D012313:RNA
references: Biopolymers. 1976 May;15(5):859-78
references: 1260107
references: IEEE Trans Pattern Anal Mach Intell. 1987 May;9(5):698-700
references: 21869429
references: Structure. 2000 Jul 15;8(7):719-27
references: 10903943
references: J Comput Biol. 1998 Fall;5(3):409-22
references: 9773341
references: Nucleic Acids Res. 2003 Nov 1;31(21):6249-57
references: 14576313
references: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references: 10592235
references: J Biol Chem. 1982 Dec 25;257(24):14686-707
references: 7174662
references: Nat Struct Biol. 2001 Nov;8(11):968-73
references: 11685244
references: J Mol Biol. 1998 Dec 18;284(5):1465-78
references: 9878364
references: Nucleic Acids Res. 2003 Feb 1;31(3):1075-85
references: 12560506
references: J Mol Biol. 2002 Jul 12;320(3):455-74
references: 12096903
references: Nat Struct Mol Biol. 2005 Oct;12(10):931-2
references: 16155581
references: Science. 2000 Aug 11;289(5481):905-20
references: 10937989
references: Nucleic Acids Res. 2004;32(8):2342-52
references: 15121895
references: Cell. 2002 Feb 22;108(4):557-72
references: 11909526
references: EMBO J. 2005 Oct 19;24(20):3576-87
references: 16193062
references: Nucleic Acids Res. 2003 Aug 15;31(16):4755-61
references: 12907716
references: RNA. 2001 Apr;7(4):499-512
references: 11345429
references: Eur J Biochem. 2000 Apr;267(8):2397-408
references: 10759866
references: Nucleic Acids Res. 2006;34(5):1481-91
references: 16531589
references: J Mol Graph. 1996 Feb;14(1):51-5, 29-32
references: 8744573
references: J Mol Biol. 2001 Oct 12;313(1):229-37
references: 11601858
references: Nucleic Acids Res. 2003 Feb 1;31(3):1086-96
references: 12560507
references: Nucleic Acids Res. 2003 Dec 1;31(23):6806-18
references: 14627814
references: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D182-4
references: 14681389
references: EMBO J. 2001 Aug 1;20(15):4214-21
references: 11483524
references: J Mol Biol. 1999 Aug 13;291(2):313-27
references: 10438623
references: Nucleic Acids Res. 1982 Feb 11;10(3):777-87
references: 7063420
references: Biochem Soc Trans. 2002 Nov;30(Pt 6):1162-6
references: 12440996
references: Science. 1996 Sep 20;273(5282):1696-9
references: 8781229
references: J Biomol Struct Dyn. 1986 Aug;4(1):49-67
references: 3271435
references: RNA. 2003 Jan;9(1):44-51
references: 12554875
references: Biopolymers. 1983 Sep;22(9):2961-76
references: 6626696
references: J Mol Biol. 2005 Aug 5;351(1):26-38
references: 15993894
references: RNA. 2004 Dec;10(12):1852-4
references: 15547133
references: Nucleic Acids Res. 2004;32(5):1666-77
references: 15016910
references: J Mol Biol. 1963 Jul;7:95-9
references: 13990617
references: J Mol Biol. 2001 May 18;308(5):919-36
references: 11352582
references: RNA. 2005 Dec;11(12):1884-97
references: 16251382
references: Electrophoresis. 1997 Dec;18(15):2714-23
references: 9504803
references: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):13904-9
references: 14612579
references: Nucleic Acids Res. 2004;32(22):6650-9
references: 15608296
references: FASEB J. 1993 Jan;7(1):97-105
references: 7678567
references: Nat Struct Mol Biol. 2004 Feb;11(2):187-92
references: 14745440
references: Nucleic Acids Res. 2003 Oct 1;31(19):5607-16
references: 14500824
references: J Mol Biol. 1978 Aug 25;123(4):631-60
references: 357743
references: EMBO J. 2000 Nov 1;19(21):5599-610
references: 11060012
references: J Mol Biol. 2004 Jun 25;340(1):141-77
references: 15184028
references: Nat Struct Biol. 2002 Jun;9(6):431-5
references: 11992125
references: Nature. 2004 Jul 1;430(6995):45-50
references: 15175762
references: Structure. 2000 May 15;8(5):527-40
references: 10801497